Late Parasitological Failure and Subsequent Isolated Gametocytemia of Uncomplicated Plasmodium falciparum Malaria in a Returned Traveler From Ghana, 2023

Herein, we report a case of uncomplicated falciparum malaria with late parasitological failure in a 45-year-old businessman returning from Ghana. The patient visited the emergency department with high fever, headache, and dizziness. He traveled without antimalarial chemoprophylaxis. Laboratory tests led to the diagnosis of uncomplicated falciparum malaria with an initial density of 37,669 parasites per μL of blood (p/μL). The patient was treated with intravenous artesunate followed by atovaquone/proguanil. He was discharged with improved condition and decreased parasite density of 887 p/μL. However, at follow-up, parasite density increased to 7,630 p/μL despite the absence of any symptoms. Suspecting treatment failure, the patient was administered intravenous artesunate and doxycycline for seven days and then artemether/lumefantrine for three days. Blood smear was negative for asexual parasitemia after re-treatment but positive for gametocytemia until day 101 from the initial diagnosis. Overall, this case highlights the risk of late parasitological failure in patients with imported uncomplicated falciparum malaria.

Model for end-stage liver disease-3.0 vs. model for end-stage liver disease-sodium: mortality prediction in Korea

Background/Aims@#The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC. @*Methods@#A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test. @*Results@#Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01). @*Conclusions@#Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.

Diagnosis of Autoimmune Hepatitis / 대한소화기학회지

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease with an uncertain cause. The diagnosis of AIH is based on the characteristic clinical and laboratory findings (elevated liver enzyme and hypergammaglobulinemia), the presence of characteristic autoantibodies, and compatible histological abnormalities. AIH lacks a signature diagnostic marker, and the diagnosis requires the exclusion of other diseases (viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced liver injury, Wilson’s disease, and hereditary hemochromatosis). Therefore, collaboration between the clinical physician, laboratory medicine experts, and pathologists is important for a diagnosis. In December 2022, the Korean Association for the Study of the Liver (KASL) clinical practice guidelines were established. This review article summarizes the diagnosis part of these guidelines.

Changes in the Hepatitis B Surface Antigen Level According to the HBeAg Status and Drug Used in Long-term Nucleos(t)ide Analog-treated Chronic Hepatitis B Patients / 대한소화기학회지

Background/Aims@#The HBsAg levels have been used to monitor the chronic hepatitis B (CHB) treatment response to antiviral therapy.On the other hand, it is unclear if the HBsAg quantification levels at each treatment point differ according to the HBeAg status and drug in CHB patients. This study compared the changes in HBsAg in CHB patients according to the HBeAg status and treatment drugs. @*Methods@#CHB patients with at least 1 year of follow-up treatment with one drug, either entecavir (ETV) or tenofovir (TDF), were enrolled in this study. The mean HBsAg levels were measured annually for up to 6 years. A linear mixed model was used to compare the HBsAg quantification levels during the follow-up period. An independent samples t-test was used to analyze the differences in the HBsAg quantification levels at each treatment time point. @*Results@#Ninety-seven patients were enrolled in this study; 59 among them were HBeAg-positive. Two patients in the TDF group achieved HBsAg seroconversion. The HBsAg level decreased during the follow-up in the ETV and TDF groups. The HBsAg level was lower in the TDF group than the ETV group during the follow-up. On the other hand, subgroup analysis showed that this trend was the same only in the HBeAg-negative patients, not in the HBeAg-positive patients. In the HBeAg-negative patients, HBsAg level in the TDF group was significantly lower than that in the ETV group at 36, 48, and 72 months. The change in HBsAg level from the baseline increased at a decreasing rate during the follow-up in both groups. Furthermore, the change in the HBsAg level in the TDF group was significantly larger than that of the ETV group at 36 months in the HBeAg-negative patients. @*Conclusions@#Although TDF might be more efficient than ETV in reducing the HBsAg level in HBeAg-negative patients in a few years, HBsAg seroconversion occurred very rarely. A further large-scale, long-term study will be needed to confirm the antiviral effects on the HBsAg level.

The effect of nucleos(t)ide analogues on clinical outcomes of patients treated with transarterial chemoembolization and radiofrequency ablation for hepatitis B virus-related hepatocellular carcinoma

Background/Aims@#Because hepatitis B virus (HBV) replication has been known to play animportant role in cancer recurrence after curative treatment of HBV-related hepatocellularcarcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs)might decrease the recurrence rate and improve patient survival. @*Methods@#The retrospective cohort study enrolled 73 patients with chronic hepatitis B whowere treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA)with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovirdisoproxil fumarate (TDF) and entecavir (ETV), respectively. @*Results@#Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were deadduring a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazardratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B(vs. class Aon cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associatedwith HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was anindependent unfavorable prognostic factor for survival. During NAs therapy, TDF was superiorto ETV for complete viral response at 1 year after the date of combination of TACE and RFA(P=0.016). However, the risks of HCC recurrence and survival were not significantly differentbetween those treated with TDF versus ETV. @*Conclusions@#TDF was superior to ETV for achieving complete viral response. However, therecurrence and mortality after TACE and RFA for HBV-related HCC were not significantlydifferent between patients treated with TDF versus ETV.

Changes in the Hepatitis B Surface Antigen Level According to the HBeAg Status and Drug Used in Long-term Nucleos(t)ide Analog-treated Chronic Hepatitis B Patients / 대한소화기학회지

Background/Aims@#The HBsAg levels have been used to monitor the chronic hepatitis B (CHB) treatment response to antiviral therapy.On the other hand, it is unclear if the HBsAg quantification levels at each treatment point differ according to the HBeAg status and drug in CHB patients. This study compared the changes in HBsAg in CHB patients according to the HBeAg status and treatment drugs. @*Methods@#CHB patients with at least 1 year of follow-up treatment with one drug, either entecavir (ETV) or tenofovir (TDF), were enrolled in this study. The mean HBsAg levels were measured annually for up to 6 years. A linear mixed model was used to compare the HBsAg quantification levels during the follow-up period. An independent samples t-test was used to analyze the differences in the HBsAg quantification levels at each treatment time point. @*Results@#Ninety-seven patients were enrolled in this study; 59 among them were HBeAg-positive. Two patients in the TDF group achieved HBsAg seroconversion. The HBsAg level decreased during the follow-up in the ETV and TDF groups. The HBsAg level was lower in the TDF group than the ETV group during the follow-up. On the other hand, subgroup analysis showed that this trend was the same only in the HBeAg-negative patients, not in the HBeAg-positive patients. In the HBeAg-negative patients, HBsAg level in the TDF group was significantly lower than that in the ETV group at 36, 48, and 72 months. The change in HBsAg level from the baseline increased at a decreasing rate during the follow-up in both groups. Furthermore, the change in the HBsAg level in the TDF group was significantly larger than that of the ETV group at 36 months in the HBeAg-negative patients. @*Conclusions@#Although TDF might be more efficient than ETV in reducing the HBsAg level in HBeAg-negative patients in a few years, HBsAg seroconversion occurred very rarely. A further large-scale, long-term study will be needed to confirm the antiviral effects on the HBsAg level.

The effect of nucleos(t)ide analogues on clinical outcomes of patients treated with transarterial chemoembolization and radiofrequency ablation for hepatitis B virus-related hepatocellular carcinoma

Background/Aims@#Because hepatitis B virus (HBV) replication has been known to play animportant role in cancer recurrence after curative treatment of HBV-related hepatocellularcarcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs)might decrease the recurrence rate and improve patient survival. @*Methods@#The retrospective cohort study enrolled 73 patients with chronic hepatitis B whowere treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA)with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovirdisoproxil fumarate (TDF) and entecavir (ETV), respectively. @*Results@#Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were deadduring a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazardratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B(vs. class Aon cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associatedwith HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was anindependent unfavorable prognostic factor for survival. During NAs therapy, TDF was superiorto ETV for complete viral response at 1 year after the date of combination of TACE and RFA(P=0.016). However, the risks of HCC recurrence and survival were not significantly differentbetween those treated with TDF versus ETV. @*Conclusions@#TDF was superior to ETV for achieving complete viral response. However, therecurrence and mortality after TACE and RFA for HBV-related HCC were not significantlydifferent between patients treated with TDF versus ETV.

Comparison of the efficacy and safety of direct-acting antiviral therapy with or without hepatitis C-related hepatocellular carcinoma

Chronic hepatitis C (CHC) treatment has dramatically improved since direct-acting antiviral (DAA) therapy was introduced. However, the use of DAA therapy in CHC patients with hepatocellular carcinoma (HCC) remains controversial. We investigated the DAA treatment response in CHC patients with HCC. Methods: We retrospectively analyzed CHC patients treated with DAA from 2016 to 2018. Patients were divided into two groups based on their HCC-history before DAA therapy. Baseline characteristics, sustained virologic response at 12 weeks (SVR 12), and HCC recurrence after DAA therapy were evaluated. We also used propensity score matching (PSM) in a 2:1 ratio to reduce confounding variables. Results: A total of 192 patients were enrolled; 78.1% were treatment-naïve, and 34.9% had liver cirrhosis (LC). Among these patients, 168 did not have HCC, and 24 had HCC. The HCC group was older (57.0 years vs. 72.0 years, p < 0.001), had a higher incidence of LC (26.2% vs. 95.8%, p < 0.001), fibrosis-4 index (2.6 vs. 9.2, p < 0.001), liver stiffness measurement (7.0 kPa vs. 17.4 kPa, p = 0.012), and α-fetoprotein (4.4 ng/mL vs. 8.2 ng/mL, p ≤ 0.001). The SVR 12 rate was 97.0% in the non- HCC group and 91.7% in the HCC group (p = 0.213). HCC recurrence was observed in 14 patients (58.3%) in the HCC group. Conclusions: DAA treatment efficacy in CHC patients with or those without HCC were not significantly different, and HCC recurrence was relatively common.

Changing Trends in Liver Cirrhosis Etiology and Severity in Korea:the Increasing Impact of Alcohol

Background@#Chronic hepatitis B is the most common cause of liver cirrhosis in South Korea. However, alcoholic liver disease has shown an increasing trend. Although the clinical implications surrounding liver cirrhosis have been changing over the years, few studies have recently examined cirrhosis epidemiology. Therefore, we aimed to investigate changes in liver cirrhosis etiology and severity in Korea. @*Methods@#We retrospectively reviewed 16,888 records of cirrhotic patients from six tertiary hospitals in Korea from 2008 to 2017. Continuous and non-continuous variables were processed via linear and Poisson regression, expressed as beta (B) coefficients and as exponentiated values of coefficients (Exp[B]), respectively. @*Results@#Chronic hepatitis B showed a decreasing trend (Exp[B] = 0.975, P < 0.001), whereas alcohol showed an increasing trend (Exp[B] = 1.013, P = 0.003), occupying the most common etiology in 2017. The Child-Turcotte-Pugh (CTP) score and decompensated liver cirrhosis prevalence did not change over the 10-year period. The incidence of variceal bleeding, severe ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis significantly decreased from 12.3% to 7.7%, 7.8% to 4.1%, 1.0% to 0.5%, and 1.9% to 1.1%, respectively (P < 0.05 for all). In the subgroup analysis, the chronic hepatitis B group showed improving CTP scores (B = −0.025, P < 0.001) and decreasing decompensated liver cirrhosis rates (Exp[B] = 0.977, P = 0.016), whereas the alcohol group demonstrated increasing CTP class C (Exp[B] = 1.031, P = 0.005) and model for end-stage liver disease scores (B = 0.081, P = 0.005) over 10 years. @*Conclusion@#The chronic hepatitis B group exhibited improved results, whereas the alcohol group still presented poor liver functions and outcomes. Future national policies and systematic approaches addressing the incidence, prevention, and treatment of alcoholic liver cirrhosis are indispensable.

Changing Trends in Liver Cirrhosis Etiology and Severity in Korea:the Increasing Impact of Alcohol

Background@#Chronic hepatitis B is the most common cause of liver cirrhosis in South Korea. However, alcoholic liver disease has shown an increasing trend. Although the clinical implications surrounding liver cirrhosis have been changing over the years, few studies have recently examined cirrhosis epidemiology. Therefore, we aimed to investigate changes in liver cirrhosis etiology and severity in Korea. @*Methods@#We retrospectively reviewed 16,888 records of cirrhotic patients from six tertiary hospitals in Korea from 2008 to 2017. Continuous and non-continuous variables were processed via linear and Poisson regression, expressed as beta (B) coefficients and as exponentiated values of coefficients (Exp[B]), respectively. @*Results@#Chronic hepatitis B showed a decreasing trend (Exp[B] = 0.975, P < 0.001), whereas alcohol showed an increasing trend (Exp[B] = 1.013, P = 0.003), occupying the most common etiology in 2017. The Child-Turcotte-Pugh (CTP) score and decompensated liver cirrhosis prevalence did not change over the 10-year period. The incidence of variceal bleeding, severe ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis significantly decreased from 12.3% to 7.7%, 7.8% to 4.1%, 1.0% to 0.5%, and 1.9% to 1.1%, respectively (P < 0.05 for all). In the subgroup analysis, the chronic hepatitis B group showed improving CTP scores (B = −0.025, P < 0.001) and decreasing decompensated liver cirrhosis rates (Exp[B] = 0.977, P = 0.016), whereas the alcohol group demonstrated increasing CTP class C (Exp[B] = 1.031, P = 0.005) and model for end-stage liver disease scores (B = 0.081, P = 0.005) over 10 years. @*Conclusion@#The chronic hepatitis B group exhibited improved results, whereas the alcohol group still presented poor liver functions and outcomes. Future national policies and systematic approaches addressing the incidence, prevention, and treatment of alcoholic liver cirrhosis are indispensable.

Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis

Background/Aims@#The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. @*Methods@#A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. @*Results@#After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. @*Conclusions@#PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.

Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis

Background/Aims@#The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. @*Methods@#A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. @*Results@#After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. @*Conclusions@#PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.

Risk Factors for Liver Function Deterioration after Transarterial Chemoembolization Refractoriness in Child-Pugh Class A Hepatocellular Carcinoma Patients / 대한소화기학회지

BACKGROUND/AIMS: A switch to systemic therapy, such as sorafenib, should be considered for hepatocellular carcinoma (HCC) patients refractory to transarterial chemoembolization (TACE). On the other hand, treatment changes are difficult if the liver function worsens to Child-Pugh B or C. Therefore, predicting the risk factors for non-responsiveness to TACE and deteriorating liver function may be helpful.METHODS: Newly diagnosed Child-Pugh A HCC patients who underwent TACE from January 2012 to June 2018 were included. After 1 year, this study evaluated whether there was a treatment response to TACE and whether the Child-Pugh class had worsened.RESULTS: Among 121 patients, 65 were refractory and 56 responded to TACE. In multivariable logistic regression analysis, the tumor size, tumor number, and albumin at the time of the diagnosis of HCC were significant prognostic factors for the treatment response to TACE. Among 65 patients who presented TACE-refractoriness, 27 showed liver function deterioration from Child-Pugh class A to class B or C after TACE. In multivariable logistic regression analysis, bilirubin at the diagnosis of HCC was a significant prognostic factor for liver function deterioration. A predictive algorithm based on the regression equations revealed a sensitivity, specificity, positive predictive value, and negative predictive value of 74.1%, 74.5%, 45.5%, and 90.9%, respectively, for TACE-refractoriness and liver function deterioration.CONCLUSIONS: The prognostic model incorporating the tumor size, tumor number, albumin, and bilirubin at the diagnosis of HCC may help identify patients who show a poor response to TACE and aggravation of liver function after TACE, who may benefit from early switching into systemic therapy before liver function aggravation.

Clinical Score System to Differentiate Severe Fever with Thrombocytopenia Syndrome Patients from Patients with Scrub Typhus or Hemorrhagic Fever with Renal Syndrome in Korea

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality in East Asia. This study aimed to develop, for primary care providers, a prediction score using initial symptoms and basic laboratory blood tests to differentiate between SFTS and other endemic zoonoses in Korea.METHODS: Patients aged ≥ 18 years diagnosed with endemic zoonoses during a 3-year period (between January 2015 and December 2017) were retrospectively enrolled from 4 tertiary university hospitals. A prediction score was built based on multivariate logistic regression analyses.RESULTS: Of 84 patients, 35 with SFTS and 49 with other endemic zoonoses were enrolled. In multivariate logistic regression analysis, independent predictors of SFTS included neurologic symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 2.173–76.747), diarrhea (OR, 10.306; 95% CI, 1.588–66.895), leukopenia (< 4,000/mm3) (OR, 19.400; 95% CI, 3.290–114.408), and normal C-reactive protein (< 0.5 mg/dL) (OR, 24.739; 95% CI, 1.812–337.742). We set up a prediction score by assigning one point to each of these four predictors. A score of ≥ 2 had 82.9% sensitivity (95% CI, 71.7%–87.5%) and 95.9% specificity (95% CI, 88.0%–99.2%). The area under the curve of the clinical prediction score was 0.950 (95% CI, 0.903–0.997).CONCLUSION: This study finding suggests a simple and useful scoring system to predict SFTS in patients with endemic zoonoses. We expect this strategic approach to facilitate early differentiation of SFTS from other endemic zoonoses, especially by primary care providers, and to improve the clinical outcomes.

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19

Background@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. @*Methods@#All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. @*Results@#The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). @*Conclusion@#The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

Clinical Score System to Differentiate Severe Fever with Thrombocytopenia Syndrome Patients from Patients with Scrub Typhus or Hemorrhagic Fever with Renal Syndrome in Korea

BACKGROUND@#Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality in East Asia. This study aimed to develop, for primary care providers, a prediction score using initial symptoms and basic laboratory blood tests to differentiate between SFTS and other endemic zoonoses in Korea.@*METHODS@#Patients aged ≥ 18 years diagnosed with endemic zoonoses during a 3-year period (between January 2015 and December 2017) were retrospectively enrolled from 4 tertiary university hospitals. A prediction score was built based on multivariate logistic regression analyses.@*RESULTS@#Of 84 patients, 35 with SFTS and 49 with other endemic zoonoses were enrolled. In multivariate logistic regression analysis, independent predictors of SFTS included neurologic symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 2.173–76.747), diarrhea (OR, 10.306; 95% CI, 1.588–66.895), leukopenia (< 4,000/mm3) (OR, 19.400; 95% CI, 3.290–114.408), and normal C-reactive protein (< 0.5 mg/dL) (OR, 24.739; 95% CI, 1.812–337.742). We set up a prediction score by assigning one point to each of these four predictors. A score of ≥ 2 had 82.9% sensitivity (95% CI, 71.7%–87.5%) and 95.9% specificity (95% CI, 88.0%–99.2%). The area under the curve of the clinical prediction score was 0.950 (95% CI, 0.903–0.997).@*CONCLUSION@#This study finding suggests a simple and useful scoring system to predict SFTS in patients with endemic zoonoses. We expect this strategic approach to facilitate early differentiation of SFTS from other endemic zoonoses, especially by primary care providers, and to improve the clinical outcomes.

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19

Background@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. @*Methods@#All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. @*Results@#The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). @*Conclusion@#The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

Clinical Score System to Differentiate Severe Fever with Thrombocytopenia Syndrome Patients from Patients with Scrub Typhus or Hemorrhagic Fever with Renal Syndrome in Korea

BACKGROUND@#Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality in East Asia. This study aimed to develop, for primary care providers, a prediction score using initial symptoms and basic laboratory blood tests to differentiate between SFTS and other endemic zoonoses in Korea.@*METHODS@#Patients aged ≥ 18 years diagnosed with endemic zoonoses during a 3-year period (between January 2015 and December 2017) were retrospectively enrolled from 4 tertiary university hospitals. A prediction score was built based on multivariate logistic regression analyses.@*RESULTS@#Of 84 patients, 35 with SFTS and 49 with other endemic zoonoses were enrolled. In multivariate logistic regression analysis, independent predictors of SFTS included neurologic symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 2.173–76.747), diarrhea (OR, 10.306; 95% CI, 1.588–66.895), leukopenia (< 4,000/mm3) (OR, 19.400; 95% CI, 3.290–114.408), and normal C-reactive protein (< 0.5 mg/dL) (OR, 24.739; 95% CI, 1.812–337.742). We set up a prediction score by assigning one point to each of these four predictors. A score of ≥ 2 had 82.9% sensitivity (95% CI, 71.7%–87.5%) and 95.9% specificity (95% CI, 88.0%–99.2%). The area under the curve of the clinical prediction score was 0.950 (95% CI, 0.903–0.997).@*CONCLUSION@#This study finding suggests a simple and useful scoring system to predict SFTS in patients with endemic zoonoses. We expect this strategic approach to facilitate early differentiation of SFTS from other endemic zoonoses, especially by primary care providers, and to improve the clinical outcomes.

An Imported Case of Disseminated Echinococcosis in Korea

A complicated case of echinococcosis with multiple organ involvement is reported in a 53-year-old businessman who frequently traveled overseas, including China, Russia, and Kazakhstan from 2001 to 2007. The patient was first diagnosed with a large liver cyst during a screening abdomen ultrasonography in 2011, but he did not follow up on the lesion afterwards. Six years later, dizziness, dysarthria, and cough developed, and cystic lesions were found in the brain, liver and lungs. The clinical course was complicated when the patient went through multiple surgeries and inadequate treatment with a short duration of albendazole without a definite diagnosis. The patient visited our hospital for the first time in August 2018 due to worsening symptoms; he was finally diagnosed with echinococcosis using imaging and serologic criteria. He is now on prolonged albendazole treatment (400 mg twice a day) with gradual clinical and radiological improvement. A high index of suspicion is warranted to early diagnose echinococcosis in a patient with a travel history to endemic areas of echinococcosis.

Co-Infection of Scrub Typhus and Human Granulocytic Anaplasmosis in Korea, 2006

BACKGROUND: Scrub typhus, severe fever with thrombocytopenia syndrome (SFTS) and human granulocytic anaplasmosis (HGA) are important arthropod-borne infectious diseases in Korea and share a common point that they are transmitted by arthropod bites mostly during outdoor activities and there are considerable overlaps of epidemiologic and clinical features at presentation. We investigated the co-infection of these infections. METHODS: The study subjects were patients with laboratory-confirmed scrub typhus who were enrolled retrospectively in 2006. SFTS virus (SFTSV) infection was confirmed by a reverse transcriptase polymerase chain reaction (PCR) to amplify partial L segment of SFTSV for molecular diagnosis. HGA was confirmed by a nested PCR to amplify 16S rRNA gene of Anaplasma phagocytophilum. Direct sequencing of the positive PCR products was performed. Clinical features of co-infected subjects were described. RESULTS: One-hundred sixty-seven patients with scrub typhus were included in the analysis. Co-infection of A. phagocytophilum was identified in 4.2% of scrub typhus patients (7/167). The route of co-infection was uncertain. The co-infected patients had not different clinical manifestations compared to the patients with scrub typhus only. All the study subjects were negative for SFTSV. CONCLUSION: We found retrospective molecular evidence of the co-infection of scrub typhus and HGA in Korea. HGA may be more prevalent than expected and need to be considered as an important differential diagnosis of febrile patients in Korea.