The Role of Age in Subclinical Atherosclerosis in Asian People Living with Human Immunodeficiency Virus / 감염과화학요법

Background@#People living with human immunodeficiency virus (PLHIV) have an increased risk of atherosclerosis and cardiovascular disease, but specific guidance on when to suspect the onset of these diseases is limited. @*Materials and Methods@#We aimed to identify cardiovascular risk factors in PLHIV using carotid intima-media thickness (IMT) through a cross-sectional, retrospective cohort study that enrolled 217 PLHIV who underwent carotid IMT measurement at a teaching hospital in Korea. We compared clinical characteristics between PLHIV with subclinical atherosclerosis and PLHIV with IMT within the normal range, and used a receiver operating characteristic curve to determine the cut-off age for predicting subclinical atherosclerosis. @*Results@#Among the study population, 115 participants (53.0%) had subclinical atherosclerosis. In logistic regression, age and dyslipidemia were significantly associated with increased carotid IMT even after adjusting for other variables (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.06 - 1.15, P <0.001; OR: 3.92, 95% CI: 1.87 - 8.22, P <0.001, respectively). The cut-off age for predicting subclinical atherosclerosis was 39.5 years (area under the curve 0.78, 95% CI: 0.72 - 0.84, P <0.001). @*Conclusion@#Conventional risk factors including age and dyslipidemia were associated with subclinical atherosclerosis in Asian PLHIV. In particular, Asian PLHIV older than 40 years had an increased risk of subclinical atherosclerosis and may benefit from carotid IMT screening.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis / 감염과화학요법

Background@#Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. @*Results@#The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). @*Conclusion@#The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis / 감염과화학요법

Background@#Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. @*Results@#The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). @*Conclusion@#The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Heterologous Vaccination for Preparing COVID-19 Pandemic / 대한내과학회지

Infectious disease pandemics are characterized by extreme uncertainty. From the more predictable response to seasonal influenza, which occurs each year, we have learned the importance of effective universal vaccines and therapeutic agents to protect high-risk groups. Heterologous vaccination with different types of vaccines to prevent COVID-19 is already recommended for various reasons: shortages of mass vaccine supply; critical adverse events, and potential superior efficacy as a booster dose. However, very few studies have examined the efficacy and safety of heterologous vaccination with mixed types. This review discusses the efficacy of vaccines currently approved in the Republic of Korea, including heterologous vaccination options.

Previous Long-term Care Facility Admission as a Risk Factor for Scabies in a Medical Facility

The study aimed to elucidate simple and effective risk factors for scabies infection in the medical environment for early detection and prevention of exposure to other patients and medical staff. We conducted a case-control study of patients who were diagnosed with scabies among hospitalized patients between 2008 and 2019 in an acute-care teaching hospital. Each case was matched according to sex and age with two randomly selected controls without scabies during hospitalization. Clinical characteristics of cases at the time of hospital admission were compared to those of the control group. The scabies group included 34 patients and 68 patients who were included in the control group. After adjusting for confounding factors, previous long-term care facility admission was only associated with scabies (adjusted odds ratio, 5.44; 95% confidence interval, 1.46–20.27; P = 0.012). Careful examination, particularly for patients with previous long-term care facility admission, might be useful for the early detection of scabies.

Infectious Diseases Physician Workforce in Korea

This study aimed to evaluate the infectious disease (ID) physician workforce in Korea. We investigated the acquisition of ID physicians from 1992 to 2019 with their current working place in the Health Care System. We defined ID physicians working at general or tertiarycare hospitals as active ID physicians. A total 275 physicians acquired ID as a sub-specialty.Among the 275, 242 were active ID physicians. The density of active ID physicians was 0.47 per 100,000 population. Of all the 17 administrative districts, 11 (64.7%) fell short of 0.47, and 131 medical institutions employed the service of ID physicians. The median number of beds per adult ID physician was 372 (interquartile range, 280–507). It is essential to secure human resources to respond to emerging infectious diseases and perform the inherent work of ID physicians.

Infectious Diseases Physician Workforce in Korea

This study aimed to evaluate the infectious disease (ID) physician workforce in Korea. We investigated the acquisition of ID physicians from 1992 to 2019 with their current working place in the Health Care System. We defined ID physicians working at general or tertiarycare hospitals as active ID physicians. A total 275 physicians acquired ID as a sub-specialty.Among the 275, 242 were active ID physicians. The density of active ID physicians was 0.47 per 100,000 population. Of all the 17 administrative districts, 11 (64.7%) fell short of 0.47, and 131 medical institutions employed the service of ID physicians. The median number of beds per adult ID physician was 372 (interquartile range, 280–507). It is essential to secure human resources to respond to emerging infectious diseases and perform the inherent work of ID physicians.

Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs

There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. We determined duration of SARS-CoV-2 virus shedding in symptomatic patients after remission of symptoms. We investigated the duration of SARS-CoV-2 RNA detection using real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or sputum or saliva. Six patients were included in the final analysis. The median (range) duration of SARS-CoV-2 viral detection after hospitalization was 34 days (22 to 67). After resolution of symptoms/signs, SARS-CoV-2 RNA was detected for median (range) of 26 days (9 to 48). Among the six patients, one had persistent detection of SARS-CoV-2 RNA until day 67 of hospitalization, which was 30 days after symptom resolution. This case represents the longest duration of SARS-CoV-2 detection, and highlights the need for long-term follow up of COVID-19 patients despite resolution of symptoms to confirm SARS-CoV-2 clearance.

Screening and Treatment of Latent Tuberculosis Infection among Healthcare Workers at a Referral Hospital in Korea / 감염과화학요법

BACKGROUND@#Healthcare workers (HCWs) have a high risk of tuberculosis (TB) infection. Since August 2017, Korea has mandated the testing of latent TB infection (LTBI) and recommended treatment from HCWs at medical institutions. However, the acceptance/completion rate and adverse events of LTBI treatment have not been analyzed.@*MATERIALS AND METHODS@#From February to August 2017, we conducted a retrospective study at a referral university hospital in Korea, to screen the interferon-gamma release assay (IGRA) tests conducted for all HCWs for detecting and treating LTBI. HCWs diagnosed with LTBI were offered a 9-month isoniazid (9H), 3-month isoniazid/rifampin (3HR), or 4-month rifampin regimen. We investigated the acceptance/completion rate, adverse events, and causes of discontinuation or change in LTBI medication. A major adverse event was one wherein a patient had any adverse event ≥grade 3 causing LTBI treatment interruption.@*RESULTS@#Of the 1,538 HCWs, 1,379 underwent IGRA testing for LTBI. Among them, 13.6% (187/1,379) tested positive and 73.3% (137/187) received treatment. The overall completion rate was 97.8% (134/137). HCWs were significantly more likely to complete first-line therapy with 3HR than with 9H (91.4% vs. 76.7%, P = 0.02). The most common major adverse event was hepatotoxicity (n = 7), followed by thrombocytopenia (n = 1) and anaphylactic shock (n = 1). Hepatotoxicity and hepatotoxicity (≥ grade 2) were more frequent in 9H than in 3HR (39.5% vs. 17.2%, P = 0.006 and 18.6% vs. 3.7%, P = 0.005, respectively). The median time to hepatotoxicity was 96 days (interquartile range, 20 – 103 days).@*CONCLUSION@#Completion of first-line therapy for LTBI is more likely with 3HR than with 9H. This might be related to the development of hepatotoxicity after around 3 months of treatment. Anaphylactic shock and platelet count should be carefully monitored in those receiving rifampin-containing regimens.

A Phase III Study to Evaluate the Immunogenicity and Safety of GC1107 (Adult Tetanus Diphtheria Vaccine) in Healthy Adults

BACKGROUND: This study was conducted to assess the immunogenicity and safety of GC1107 (adult tetanus diphtheria [Td] vaccine). The primary goal was to evaluate the non-inferiority of the immunogenicity of GC1107 compared to the control vaccine. Additionally, the safety profiles of GC1107 and the control vaccine were compared. METHODS: The subjects were adults ≥ 18 years old who were not injected with Td or adult tetanus-diphtheria-pertussis (TdaP) vaccine within the recent 5 years. A total of 253 subjects were enrolled and randomized to either the GC1107 group or the control group. For immunogenicity assessment, blood samples were collected at baseline and 28 days after vaccination and antibody titer of diphtheria and tetanus were assessed. RESULTS: The seroprotection rates of diphtheria and tetanus were 89.76% and 91.34%, respectively, in the GC1107 group, and 87.80% and 86.99% in the control group. The geometric mean titer (GMT) of the anti-diphtheria antibody increased after vaccination in both groups, showing no significant difference between the groups (P = 0.139). The anti-tetanus GMTs after vaccination also showed comparable increases in both groups, and showed no significant difference (P = 0.860). In the safety evaluation, solicited local adverse reactions occurred in 81.2% of the subjects in the GC1107 group and in 86.4% of the subjects in the control group. Solicited systemic adverse events occurred in 33.2% of the subjects in the GC1107 group and in 47.2% of the subjects in the control group, which did not reach statistical significance. CONCLUSION: This phase III study demonstrated non-inferiority in immunogenicity and comparable safety of GC1107 compared with the control Td vaccine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02361866

Aggressive Contact Investigation of In-Hospital Exposure to Active Pulmonary Tuberculosis

BACKGROUND: In-hospital detection of newly diagnosed active pulmonary tuberculosis (TB) is important for prevention of potential outbreaks. Here, we report our experience of the aggressive contact investigation strategy in a university hospital in the Republic of Korea after healthcare workers (HCWs), patients, and visitors experience an in-hospital exposure to active pulmonary TB. METHODS: A contact investigation after the unexpected detection of newly diagnosed active pulmonary TB (index patients) was performed in a university hospital from August 2016 to April 2017. Initial and 3-month-post-exposure chest radiographs were advised for all patients, visitors, and HCWs in close contact with the index patients. An additional tuberculous skin test or interferon gamma releasing assay was performed at the time of exposure and 3 months post-exposure in HCWs in close contact with the index patients. RESULTS: Twenty-four index patients were unexpectedly diagnosed with active pulmonary TB after admission to the hospital with unassociated diseases. The median time from admission to TB diagnosis was 5 days (range, 1–22 days). In total, 1,057 people were investigated because of contact with the index patients, 528 of which had close contact (206 events in 157 HCWs, 322 patients or visitors). Three months post exposure, 9 (9.2%) among 98 TB-naïve close contact HCWs developed latent tuberculosis infections (LTBIs). Among the 65 close contact patients or visitors, there was no radiological or clinical evidence of active pulmonary TB. CONCLUSION: An aggressive contact investigation after an unexpected in-hospital diagnosis of active pulmonary TB revealed a high incidence of LTBI among TB-naïve HCWs who had contact with the index patients.

Early Intravenous Colistin Therapy as a Favorable Prognostic Factor for 28-day Mortality in Patients with CRAB Bacteremia: a Multicenter Propensity Score-Matching Analysis

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with high mortality. One of the strategies to reduce the mortality in patients with CRAB infections is to use intravenous colistin early but the effect of this strategy has not been proven. Therefore, we investigated the association of early colistin therapy with 28-day mortality in patients with CRAB bacteremia. METHODS: This retrospective multicenter propensity score-matching analysis was conducted in the Korea by reviewing the medical records of adult patients with CRAB bacteremia between January 2012 and March 2015. Early colistin therapy was defined as intravenous colistin administration for > 48 hours within five days after the blood culture collection. To identify the risk factors associated with the 28-day mortality in CRAB bacteremia, the clinical variables of the surviving patients were compared to those of the deceased patients. RESULTS: Of 303 enrolled patients, seventy-six (25.1%) patients received early colistin therapy. The 28-day mortality was 61.4% (186/303). Fatal or rapidly-fatal McCabe classifications, intensive care unit admission, Sequential Organ Failure Assessment scores ≥ 8, vasopressor use, and acute kidney injury were statistically independent poor prognostic factors. Catheter-related infection and early colistin therapy (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.21–0.94) were independent favorable prognostic factors associated with 28-day mortality in patients with CRAB bacteremia. Early colistin therapy was still significantly associated with lower 28-day mortality in the propensity score-matching analysis (aOR, 0.31; 95% CI, 0.11–0.88). CONCLUSION: This study suggests that early colistin therapy might help reduce the mortality of patients with CRAB bacteremia.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia / 감염과화학요법

BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia / 감염과화학요법

BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9 Influenza Virus Infection in Returning Travelers

Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.

Is the Initial Size of Tuberculous Lymphadenopathy associated with Lymph Node Enlargement during Treatment? / 감염과화학요법

There are little data on the changes in lymph node (LN) size during the treatment of tuberculous lymphadenopathy (TB LAP). This study aimed to provide data on LN changes during treatment. Between March 2014 and December 2015, 20 patients who were diagnosed with cervical TB LAP were enrolled. LN enlargement within two months (50%, 4/8 vs. 8.3%, 1/12; P = 0.04) was more frequently observed in patients with initial LN size ≥ 7.5 cm². Enlarged LNs were excised in three patients owing to pain and fistula formation. Initial LN size may be associated with LN enlargement during treatment.

Institutional Preparedness to Prevent Future Middle East Respiratory Syndrome Coronavirus-Like Outbreaks in Republic of Korea / 감염과화학요법

A year has passed since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea. This 2015 outbreak led to a better understanding of healthcare infection control. The first Korean patient infected by Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was diagnosed on May 20, 2015, after he returned from Qatar and Bahrain. Thereafter, 186 Korean people were infected with the MERS-CoV in a short time through human-to-human transmission. All these cases were linked to healthcare settings, and 25 (13.5 %) infected patients were healthcare workers. Phylogenetic analysis suggested that the MERS-CoV isolate found in the Korean patient was closely related to the Qatar strain, and did not harbor transmission efficiency-improving mutations. Nevertheless, with the same infecting virus strain, Korea experienced the largest MERS-CoV outbreak outside the Arabian Peninsula, primarily due to the different characteristics of population density and the healthcare system. We aimed to review the epidemiological features and existing knowledge on the Korean MERS outbreak, and suggest methods to prevent future epidemics.

Institutional preparedness for infectious diseases and improving care

The experience of the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea showed greater impact on healthcare institutions as compared to the previous epidemic in the Middle East in 2012. However, the Middle East respiratory syndrome coronavirus was biologically identical to that of 2012, without evidence of a mutation that would account for increased transmissibility. Due to the higher population density of Korea and lower medical costs, Korean hospitals are usually crowded with high numbers of both inpatients and outpatients, who function as a reservoir for intra-hospital transmission. The fact that the patient referral system between smaller and larger hospitals is very active and efficient in Korea was one reason for high inter-hospital propagation of the Middle East respiratory syndrome outbreak. To prepare for a future epidemic in Korea, an improved contact tracing policy, improved public hospital facilities for critical care of severe infections, and pre-emptive isolation for unknown respiratory infections should be emphasized.

Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities / 감염과화학요법

Middle East Respiratory Syndrome (MERS) is an acute viral respiratory illness with high mortality caused by a new strain of betacoronavirus (MERS-CoV). Since the report of the first patient in Saudi Arabia in 2012, large-scale outbreaks through hospital-acquired infection and inter-hospital transmission have been reported. Most of the patients reported in South Korea were also infected in hospital settings. Therefore, to eliminate the spread of MERS-CoV, infection prevention and control measures should be implemented with rigor. The present guideline has been drafted on the basis of the experiences of infection control in the South Korean hospitals involved in the recent MERS outbreak and on domestic and international infection prevention and control guidelines. To ensure efficient MERS-CoV infection prevention and control, care should be taken to provide comprehensive infection control measures including contact control, hand hygiene, personal protective equipment, disinfection, and environmental cleaning.

Infective Endocarditis with Unusual Location of Vegetation in a Patient with Hemodialysis Followed by Recurrent Catheter-Related Blood Stream Infection

The incidence of infective endocarditis (IE) in hemodialysis patients is higher than the general population. Hemodialysis patients with IE have a poorer prognosis than other patients with IE. The most common sites of IE in hemodialysis patients are the mitral valve and aortic valve. A 47-year-old woman had suffered from recurrent catheter-related blood stream infection and she was strongly suspected of IE. Despite repeated transthoracic echocardiography and transesophageal echocardiography (TEE), IE was revealed several months later by TEE due to the unusual location of the vegetation. The vegetation was detected on the left ventricle outflow tract. She recovered well without any complication after mitral valve replacement surgery.