1.Status of common parasitic diseases in Korea in 2019
Journal of the Korean Medical Association 2019;62(8):437-456
		                        		
		                        			
		                        			This study aimed to determine the status of common parasitic disease in Korea in 2019. Twelve parasitic diseases were selected: toxocariasis, anisakiasis, paragonimiasis, sparganosis, cysticercosis, toxoplasmosis, clonorchiasis, enterobiasis, trichuriasis, trichomoniasis, cryptosporidiosis, and malaria. Their biology, epidemiology, pathogenesis, symptoms and signs, diagnosis, treatment, and prognosis were evaluated. Of the parasitic diseases, toxocariasis was the most prevalent according to serological results. Anisakiasis should be considered when acute gastrointestinal symptoms occur with a recent past history of raw seafood ingestion. Paragonimiasis, sparganosis, and cysticercosis can be diagnosed using an enzyme-linked immunosorbent assay; thus, enzyme-linked immunosorbent assay needs to be performed for suspected cases. Toxoplasmosis and cryptosporidiosis are opportunistic infections. The symptoms and signs are aggravated under immunocompromised conditions. Although the egg positivity rate of Clonorchis sinensis is higher than that of other intestinal parasitic diseases, encountering patients with complaints of symptoms caused by clonorchiasis is rare because the worm burden is low. Trichomoniasis is usually managed by gynecologists; therefore, it should be included in the differential diagnoses of vaginal diseases. The annual number of malaria cases has decreased, although it remains at approximately 500 cases per year. Malaria should be suspected when symptoms such as intermittent fever, headache, and splenomegaly are noted especially when the patients reside near demilitarized zones. Although the prevalence and number of reported cases of parasitic diseases have decreased in Korea, we should consider parasitic diseases in the list of differential diagnoses.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Anisakiasis
		                        			;
		                        		
		                        			Biology
		                        			;
		                        		
		                        			Clonorchiasis
		                        			;
		                        		
		                        			Clonorchis sinensis
		                        			;
		                        		
		                        			Cryptosporidiosis
		                        			;
		                        		
		                        			Cysticercosis
		                        			;
		                        		
		                        			Diagnosis
		                        			;
		                        		
		                        			Diagnosis, Differential
		                        			;
		                        		
		                        			Eating
		                        			;
		                        		
		                        			Enterobiasis
		                        			;
		                        		
		                        			Enzyme-Linked Immunosorbent Assay
		                        			;
		                        		
		                        			Epidemiology
		                        			;
		                        		
		                        			Fever
		                        			;
		                        		
		                        			Headache
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Korea
		                        			;
		                        		
		                        			Malaria
		                        			;
		                        		
		                        			Opportunistic Infections
		                        			;
		                        		
		                        			Ovum
		                        			;
		                        		
		                        			Paragonimiasis
		                        			;
		                        		
		                        			Parasitic Diseases
		                        			;
		                        		
		                        			Prevalence
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Republic of Korea
		                        			;
		                        		
		                        			Seafood
		                        			;
		                        		
		                        			Sparganosis
		                        			;
		                        		
		                        			Splenomegaly
		                        			;
		                        		
		                        			Toxocariasis
		                        			;
		                        		
		                        			Toxoplasmosis
		                        			;
		                        		
		                        			Trichuriasis
		                        			;
		                        		
		                        			Vaginal Diseases
		                        			
		                        		
		                        	
2.An Alternative Method for Extracting Plasmodium DNA from EDTA Whole Blood for Malaria Diagnosis
Krongkaew SEESUI ; Kanokwan IMTAWIL ; Phimphakon CHANETMAHUN ; Porntip LAUMMAUNWAI ; Thidarut BOONMARS
The Korean Journal of Parasitology 2018;56(1):25-32
		                        		
		                        			
		                        			Molecular techniques have been introduced for malaria diagnosis because they offer greater sensitivity and specificity than microscopic examinations. Therefore, DNA isolation methods have been developed for easy preparation and cost effectiveness. The present study described a simple protocol for Plasmodium DNA isolation from EDTA-whole blood. This study demonstrated that after heating infected blood samples with Tris–EDTA buffer and proteinase K solution, without isolation and purification steps, the supernatant can be used as a DNA template for amplification by PCR. The sensitivity of the extracted DNA of Plasmodium falciparum and Plasmodium vivax was separately analyzed by both PCR and semi-nested PCR (Sn-PCR). The results revealed that for PCR the limit of detection was 40 parasites/μl for P. falciparum and 35.2 parasites/μl for P. vivax, whereas for Sn-PCR the limit of detection was 1.6 parasites/μl for P. falciparum and 1.4 parasites/μl for P. vivax. This new method was then verified by DNA extraction of whole blood from 11 asymptomatic Myanmar migrant workers and analyzed by Sn-PCR. The results revealed that DNA can be extracted from all samples, and there were 2 positive samples for Plasmodium (P. falciparum and P. vivax). Therefore, the protocol can be an alternative method for DNA extraction in laboratories with limited resources and a lack of trained technicians for malaria diagnosis. In addition, this protocol can be applied for subclinical cases, and this will be helpful for epidemiology and control.
		                        		
		                        		
		                        		
		                        			Cost-Benefit Analysis
		                        			;
		                        		
		                        			Diagnosis
		                        			;
		                        		
		                        			DNA
		                        			;
		                        		
		                        			Edetic Acid
		                        			;
		                        		
		                        			Endopeptidase K
		                        			;
		                        		
		                        			Epidemiology
		                        			;
		                        		
		                        			Heating
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Limit of Detection
		                        			;
		                        		
		                        			Malaria
		                        			;
		                        		
		                        			Methods
		                        			;
		                        		
		                        			Myanmar
		                        			;
		                        		
		                        			Plasmodium falciparum
		                        			;
		                        		
		                        			Plasmodium vivax
		                        			;
		                        		
		                        			Plasmodium
		                        			;
		                        		
		                        			Polymerase Chain Reaction
		                        			;
		                        		
		                        			Sensitivity and Specificity
		                        			;
		                        		
		                        			Transients and Migrants
		                        			
		                        		
		                        	
3.Genetic Diversity of Plasmodium vivax Causing Epidemic Malaria in the Republic of Korea
Young Yil BAHK ; Jeonga KIM ; Seong Kyu AHN ; Byoung Kuk NA ; Jong Yil CHAI ; Tong Soo KIM
The Korean Journal of Parasitology 2018;56(6):545-552
		                        		
		                        			
		                        			Plasmodium vivax is more challenging to control and eliminate than P. falciparum due to its more asymptomatic infections with low parasite densities making diagnosis more difficult, in addition to its unique biological characteristics. The potential re-introduction of incidence cases, either through borders or via human migrations, is another major hurdle to sustained control and elimination. The Republic of Korea has experienced re-emergence of vivax malaria in 1993 but is one of the 32 malaria-eliminating countries to-date. Despite achieving successful nationwide control and elimination of vivax malaria, the evolutionary characteristics of vivax malaria isolates in the Republic of Korea have not been fully understood. In this review, we present an overview of the genetic variability of such isolates to increase understanding of the epidemiology, diversity, and dynamics of vivax populations in the Republic of Korea.
		                        		
		                        		
		                        		
		                        			Asymptomatic Infections
		                        			;
		                        		
		                        			Diagnosis
		                        			;
		                        		
		                        			Epidemiology
		                        			;
		                        		
		                        			Genetic Variation
		                        			;
		                        		
		                        			Human Migration
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Korea
		                        			;
		                        		
		                        			Malaria
		                        			;
		                        		
		                        			Malaria, Vivax
		                        			;
		                        		
		                        			Parasites
		                        			;
		                        		
		                        			Plasmodium vivax
		                        			;
		                        		
		                        			Plasmodium
		                        			;
		                        		
		                        			Population Characteristics
		                        			;
		                        		
		                        			Republic of Korea
		                        			
		                        		
		                        	
4.Plasmodium knowlesi as a Threat to Global Public Health.
Roland WESOLOWSKI ; Alina WOZNIAK ; Celestyna MILA-KIERZENKOWSKA ; Karolina SZEWCZYK-GOLEC
The Korean Journal of Parasitology 2015;53(5):575-581
		                        		
		                        			
		                        			Malaria is a tropical disease caused by protozoans of the Plasmodium genus. Delayed diagnosis and misdiagnosis are strongly associated with higher mortality. In recent years, a greater importance is attributed to Plasmodium knowlesi, a species found mainly in Southeast Asia. Routine parasitological diagnostics are associated with certain limitations and difficulties in unambiguous determination of the parasite species based only on microscopic image. Recently, molecular techniques have been increasingly used for predictive diagnosis. The aim of the study is to draw attention to the risk of travelling to knowlesi malaria endemic areas and to raise awareness among personnel involved in the therapeutic process.
		                        		
		                        		
		                        		
		                        			Asia, Southeastern
		                        			;
		                        		
		                        			Global Health
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Malaria/diagnosis/*epidemiology/*parasitology
		                        			;
		                        		
		                        			Microscopy/methods
		                        			;
		                        		
		                        			Molecular Diagnostic Techniques/methods
		                        			;
		                        		
		                        			Plasmodium knowlesi/*isolation & purification
		                        			;
		                        		
		                        			Public Health
		                        			
		                        		
		                        	
5.Evaluation of the Accuracy of the EasyTest(TM) Malaria Pf/Pan Ag, a Rapid Diagnostic Test, in Uganda.
Chom Kyu CHONG ; Pyo Yun CHO ; Byoung Kuk NA ; Seong Kyu AHN ; Jin Su KIM ; Jin Soo LEE ; Sung Keun LEE ; Eun Taek HAN ; Hak Yong KIM ; Yun Kyu PARK ; Seok Ho CHA ; Tong Soo KIM
The Korean Journal of Parasitology 2014;52(5):501-505
		                        		
		                        			
		                        			In recent years, rapid diagnostic tests (RDTs) have been widely used for malaria detection, primarily because of their simple operation, fast results, and straightforward interpretation. The Asan EasyTest(TM) Malaria Pf/Pan Ag is one of the most commonly used malaria RDTs in several countries, including Korea and India. In this study, we tested the diagnostic performance of this RDT in Uganda to evaluate its usefulness for field diagnosis of malaria in this country. Microscopic and PCR analyses, and the Asan EasyTest(TM) Malaria Pf/Pan Ag rapid diagnostic test, were performed on blood samples from 185 individuals with suspected malaria in several villages in Uganda. Compared to the microscopic analysis, the sensitivity of the RDT to detect malaria infection was 95.8% and 83.3% for Plasmodium falciparum and non-P. falciparum, respectively. Although the diagnostic sensitivity of the RDT decreased when parasitemia was < or =500 parasites/microl, it showed 96.8% sensitivity (98.4% for P. falciparum and 93.8% for non-P. falciparum) in blood samples with parasitemia > or =100 parasites/microl. The specificity of the RDT was 97.3% for P. falciparum and 97.3% for non-P. falciparum. These results collectively suggest that the accuracy of the Asan EasyTest(TM) Malaria Pf/Pan Ag makes it an effective point-of-care diagnostic tool for malaria in Uganda.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Antigens, Protozoan/blood/*isolation & purification
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Malaria, Falciparum/*diagnosis/epidemiology
		                        			;
		                        		
		                        			Parasitemia
		                        			;
		                        		
		                        			Point-of-Care Systems
		                        			;
		                        		
		                        			Predictive Value of Tests
		                        			;
		                        		
		                        			Reagent Kits, Diagnostic
		                        			;
		                        		
		                        			Sensitivity and Specificity
		                        			;
		                        		
		                        			Uganda/epidemiology
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
6.Probability of Antibody Formation against Circumsporozoite Protein of Plasmodium vivax among Korean Malaria Patients.
Ho Woo NAM ; Kyoung Ju SONG ; Hye Jin AHN ; Zhaoshou YANG ; Chom Kyu CHONG ; Pyo Yun CHO ; Seong Kyu AHN ; Tong Soo KIM
The Korean Journal of Parasitology 2014;52(2):143-149
		                        		
		                        			
		                        			To evaluate the seroprevalence against circumsporozoite protein (CSP) of Plasmodium vivax in sera of Korean patients, the central repeating domain (CRD) of CSP was cloned and analyzed. From the genomic DNA of patient's blood, 2 kinds of CSPs were identified to belong to a VK210 type, which is the dominant repeating of GDRA(D/A)GQPA, and named as PvCSPA and PvCSPB. Recombinantly expressed his-tagged PvCSPA or PvCSPB in Escherichia coli reacted well against sera of patients in western blot, with the detecting rate of 47.9% (58/121), which included 15 cases positive for PvCSPA, 6 cases positive for PvCSPB, and 37 cases for both. The mixture of PvCSPA and PvCSPB was loaded to a rapid diagnostic test kit (RDT) and applied with the same set of patient sera, which resulted in detection rates of 57.0% (69/121). When the protein sequences of PvCSPA were compared with those of P. vivax in endemic regions of India and Uganda, they were compatibly homologous to PvCSPA with minor mutations. These results suggested that the recombinant PvCSPA and PvCSPB loaded RDT may be a milestone in latent diagnosis which has been a hot issue of domestic malaria and important for radical therapy in overlapped infections with P. falciparum in tropical and subtropical areas. During the biological process of malarial infection, exposure of CSP to antigen-antibody reaction up to 57.0% is the first report in Korea.
		                        		
		                        		
		                        		
		                        			Amino Acid Sequence
		                        			;
		                        		
		                        			Antibodies, Protozoan/*blood/immunology
		                        			;
		                        		
		                        			Antibody Formation
		                        			;
		                        		
		                        			Antigens, Protozoan/immunology
		                        			;
		                        		
		                        			Base Sequence
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			India
		                        			;
		                        		
		                        			Malaria, Vivax/*diagnosis/*epidemiology/immunology
		                        			;
		                        		
		                        			Merozoite Surface Protein 1/genetics/*immunology
		                        			;
		                        		
		                        			Plasmodium vivax/genetics/immunology
		                        			;
		                        		
		                        			Protozoan Proteins/genetics/*immunology
		                        			;
		                        		
		                        			Reagent Kits, Diagnostic
		                        			;
		                        		
		                        			Recombinant Proteins/diagnostic use/immunology
		                        			;
		                        		
		                        			Republic of Korea/epidemiology
		                        			;
		                        		
		                        			Sequence Analysis, DNA
		                        			;
		                        		
		                        			Seroepidemiologic Studies
		                        			;
		                        		
		                        			Uganda
		                        			
		                        		
		                        	
7.Nested-PCR and a New ELISA-Based NovaLisa Test Kit for Malaria Diagnosis in an Endemic Area of Thailand.
Pimwan THONGDEE ; Wanna CHAIJAROENKUL ; Jiraporn KUESAP ; Kesara NA-BANGCHANG
The Korean Journal of Parasitology 2014;52(4):377-381
		                        		
		                        			
		                        			Microscopy is considered as the gold standard for malaria diagnosis although its wide application is limited by the requirement of highly experienced microscopists. PCR and serological tests provide efficient diagnostic performance and have been applied for malaria diagnosis and research. The aim of this study was to investigate the diagnostic performance of nested PCR and a recently developed an ELISA-based new rapid diagnosis test (RDT), NovaLisa test kit, for diagnosis of malaria infection, using microscopic method as the gold standard. The performance of nested-PCR as a malaria diagnostic tool is excellent with respect to its high accuracy, sensitivity, specificity, and ability to discriminate Plasmodium species. The sensitivity and specificity of nested-PCR compared with the microscopic method for detection of Plasmodium falciparum, Plasmodium vivax, and P. falciparum/P. vivax mixed infection were 71.4 vs 100%, 100 vs 98.7%, and 100 vs 95.0%, respectively. The sensitivity and specificity of the ELISA-based NovaLisa test kit compared with the microscopic method for detection of Plasmodium genus were 89.0 vs 91.6%, respectively. NovaLisa test kit provided comparable diagnostic performance. Its relatively low cost, simplicity, and rapidity enables large scale field application.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Coinfection/*diagnosis/epidemiology
		                        			;
		                        		
		                        			Endemic Diseases
		                        			;
		                        		
		                        			Enzyme-Linked Immunosorbent Assay/methods
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Malaria, Falciparum/*diagnosis/epidemiology
		                        			;
		                        		
		                        			Malaria, Vivax/*diagnosis/epidemiology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Molecular Diagnostic Techniques/*methods
		                        			;
		                        		
		                        			Polymerase Chain Reaction/*methods
		                        			;
		                        		
		                        			Sensitivity and Specificity
		                        			;
		                        		
		                        			Serologic Tests/methods
		                        			;
		                        		
		                        			Thailand/epidemiology
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
8.The proportion of fevers attributable to malaria varies significantly between sites in Papua New Guinea.
Hetzel MW ; Paul S ; Benjamin L ; Makita L ; Mueller I ; Siba PM
Papua New Guinea medical journal 2014;57(1-4):39-51
		                        		
		                        			
		                        			Malaria is endemic across lowland Papua New Guinea (PNG) and case management has been based on symptomatic diagnosis and presumptive treatment of fever cases with an antimalarial. This study aimed to investigate the prevalence of malaria infection among fever cases presenting to 5 purposely selected sentinel health facilities in order to estimate the proportion of patients requiring antimalarial drugs. A total of 1807 fever patients were screened. Overall, 45% of fever patients had a positive malaria blood slide; 35% were infected with Plasmodium falciparum, 9% with P. vivax and 2% with P. malariae. Slide positivity was highest in Dreikikir (75%) and lowest in Wipim (2%). Among patients aged 1-4 years, 22% had moderate to severe anaemia (Hb < 8 g/dI) and 21% of children 2-9 years of age showed signs of splenomegaly (Hackett score 1-5). Comorbidity differed significantly between study sites and was not closely correlated with malaria infection. Clinical diagnosis by health facility staff was malaria for 67% of all fever cases, including 89% of slide-positive and 48% of slide-negative patients. 70% of rapid diagnostic test-negative cases were treated with an antimalarial. It is estimated that due to the lack of parasitological diagnosis the selected health facilities reported an excess of 18% (Dreikikir) to 98% (Wipim) malaria patients on average each month. In consideration of the significant differences in malaria-attributable fevers between study sites, the implementation of parasitological diagnosis in health facilities and administration of antimalarials only to test-positive patients has the potential to significantly improve the management of fever cases and reporting of malaria. A better tailoring to different settings may increase the effectiveness of malaria control interventions.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			 Adult
		                        			;
		                        		
		                        			 Child
		                        			;
		                        		
		                        			 Child, Preschool
		                        			;
		                        		
		                        			 Female
		                        			;
		                        		
		                        			 Fever/*parasitology
		                        			;
		                        		
		                        			 Humans
		                        			;
		                        		
		                        			 Infant
		                        			;
		                        		
		                        			 Malaria/complications/diagnosis/*epidemiology
		                        			;
		                        		
		                        			 Male
		                        			;
		                        		
		                        			 Papua New Guinea/epidemiology
		                        			;
		                        		
		                        			 Young Adult
		                        			
		                        		
		                        	
9.Urinary schistosomiasis and malaria associated anemia in Ethiopia.
Ketema DERIBEW ; Zinaye TEKESTE ; Beyene PETROS ; Lim Boon HUAT
Asian Pacific Journal of Tropical Biomedicine 2013;3(4):307-310
OBJECTIVETo assess the prevalence of anemia in children with urinary schistosomiasis, malaria and concurrent infections by the two diseases.
METHODSUrine and blood samples were collected from 387 children (216 males and 171 females) to examine urinary schistosomiasis and malaria and to determine hemoglobin concentration at Hassoba and Hassoba Buri village in Amibara woreda, Afar region, Ethiopia.
RESULTSThe overall prevalence of urinary schistosomiasis and Plasmodium falciparum malaria was 24.54% and 6.20% respectively. Only 2.84% of children carried concurrent infections of both parasites. There was high percentage of anemic patients (81.81%) in the coinfected cases than in either malaria (33.3%) or schistosomiasis (38.94%) cases. There was significantly low mean hemoglobin concentration in concurrently infected children than non-infected and single infected (P<0.05). The mean hemoglobin concentration between Plasmodium falciparum and S. haematobium infected children showed no significant difference (P>0.05). The level of hemoglobin was negatively correlated with the number of S. haematobium eggs/10 mL urine (r=-0.6) and malaria parasitemia (r=-0.53).
CONCLUSIONSThe study showed that anemia is higher in concurrently infected children than non-infected and single infected. Furthermore, level of hemoglobin was negatively correlated with the number of S. haematobium eggs and malaria parsitemia. Therefore, examination of hemoglobin status in patients co-infected with malaria and schistosomiasis is important to reduce the risk of anemia and to improve health of the community.
Adolescent ; Anemia ; diagnosis ; epidemiology ; etiology ; Child ; Child, Preschool ; Ethiopia ; Female ; Humans ; Malaria ; complications ; Male ; Prevalence ; Schistosomiasis haematobia ; complications ; diagnosis
10.Parasitemia Characteristics of Plasmodium vivax Malaria Patients in the Republic of Korea.
Ae Jung HUH ; Yee Gyung KWAK ; Eu Suk KIM ; Kkot Sil LEE ; Joon Sup YEOM ; Yong Kyun CHO ; Chang Seok KIM ; Jae Won PARK
Journal of Korean Medical Science 2011;26(1):42-46
		                        		
		                        			
		                        			Parasitemia characteristics of Plasmodium vivax malaria in temperate regions may differ from those in tropical zones. However, most parasitological and clinical features of P. vivax malaria have been investigated in the latter. In this study, we investigated 383 malaria patients to clarify the parasitemia characteristics of a P. vivax strain in the Republic of Korea (ROK). The mean parasitemia (8,396/microL) was less than half of tropical P. vivax malaria, and multiple invasions of erythrocytes were not rare (53.5% of the patients, 2.4% of the total investigated RBCs), but less than the observations in tropical zones. The intervals between the first symptom onset and diagnosis were significantly longer in gametocyte (+) patients than in gametocyte (-) patients. Only half of the total patients had both genders of gametocytes (191 of 353), and the male gametocyte density (169/microL) was lower than that of P. vivax strains of a previous study. Multiple invasions of erythrocytes and gametocytemia were coincident factors of the degree of anemia in P. vivax malaria. The present findings demonstrate the P. vivax strain in ROK reveals relatively low parasitemia and low male to female gametocyte ratio. The low ratio may be related with low transmission efficacy.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Erythrocytes/parasitology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Malaria, Vivax/*diagnosis/epidemiology/parasitology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Parasitemia/*diagnosis/epidemiology/parasitology
		                        			;
		                        		
		                        			Plasmodium vivax/isolation & purification
		                        			;
		                        		
		                        			Republic of Korea/epidemiology
		                        			
		                        		
		                        	
            

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