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There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination. Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4+ or CD8+ T cells. A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4+ T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group. Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions. [ABSTRACT FROM AUTHOR]

We report on a patient with severe fever with thrombocytopenia syndrome who fully recovered. Imaging with 2-deoxy-2-fluoro-glucose positron emission tomography showed hypermetabolism in regional lymph nodes and the spleen. Histopathological findings of affected lymph nodes showed subacute necrotizing lymphadenitis and the presence of virus-infected cells. [ABSTRACT FROM AUTHOR]

Background Patient participation in hand hygiene programs is regarded as an important component of hand hygiene improvement, but the feasibility of the program is still largely unknown. We examined the perceptions of patients/families and health care workers (HCWs) with regard to patient participation in hand hygiene. Methods A cross-sectional survey of patients/families as well as physicians and nurses was performed using an anonymous, self-administered questionnaire in a 1,000-bed teaching hospital in South Korea. Results A total of 152 physicians, 387 nurses, and 334 patients/families completed the survey. The overall response rate was 84%, 85%, and more than 60% among physicians, nurses, and patients/families, respectively. Whereas 75% of patients/families wished to ask HCWs to clean their hands if they did not do so themselves, only 26% of physicians and 31% of nurses supported the participation of patients ( P < .001). The most common reason why HCWs disagreed with patient participation was concern about negative effects on their relationship with patients (54%). Regarding the method of patient involvement, patients preferred to assess hand hygiene performance, whereas physicians preferred patients to ask directly. Conclusions There was a significant discrepancy in perceptions regarding patient participation between patients/families and HCWs. Enhanced understanding and acceptance of any new program by both patients and HCWs before its introduction are needed for successful implementation. [ABSTRACT FROM AUTHOR]

Summary: Objective: To investigate the risk factors for late presentation in the Republic of Korea, where massive mandatory screening for HIV infection was conducted by the government until the late 1990s. Methods: Data over the period 1987–2008 were analyzed from HIV patients for whom records of CD4 cell counts within 3 months of HIV diagnosis were available. Using multivariate logistic regression analysis including demographic and clinical variables, we examined factors associated with late presentation, defined as having a CD4 cell count of less than 200 cells/mm3 at the time of diagnosis. Results: Of a total of 994 patients with a new diagnosis of HIV infection, 405 (41%) were late presenters. As the proportion of patients diagnosed by mandatory screening decreased over time (31% in 1987–1998 versus 8% in 1999–2008, P < 0.001), the proportion of late presenters increased (31% in 1987–1998 versus 43% in 1999–2008, P = 0.007). The independent risk factors for late presentation were older age (adjusted odds ratio [aOR], per increase of 10 years, 1.31; 95% confidence interval [CI], 1.15–1.49; P < 0.001), male sex (aOR, 1.74; 95% CI, 1.03–2.95; P = 0.040), negativity for VDRL (aOR, 1.58; 95% CI, 1.16–2.14; P = 0.003), and diagnosis after 1999 (aOR, 1.64; 95% CI, 1.05–2.56; P = 0.031). Conclusions: Older age, male sex, negativity for VDRL, and diagnosis after 1999, were associated with late presentation, and the proportion of late presenters increased after the mandatory testing policy was abolished. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the incidence, risk factors and outcomes for anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic liver disease including cirrhosis. Methods: A total of 107 patients with chronic liver disease were assessed for anti-TB DILI. Anti-TB DILI was defined as elevation of alkaline phosphatase (ALP), aspartate transaminase, or alanine transaminase, or an increase in Child-Turcotte-Pugh score within 2 months of initiating anti-TB medication. The risk factors for anti-TB DILI were evaluated by multivariate logistic regression analysis. Results: Fifty-eight (54%) patients had cirrhosis. Of 93 patients receiving one or more hepatotoxic anti-TB drugs, 18 (17%) experienced DILI: 11 (24%) among 46 patients with chronic hepatitis and 7 (15%) among 46 patients with compensated liver cirrhosis (P = 0.271). Independent risk factors for DILI were female sex, number of hepatotoxic anti-TB drugs administered and baseline ALP levels but not cirrhosis itself. Of the 18 patients with DILI, 13 (72%) successfully completed anti-TB treatment after switching to less hepatotoxic drug regimens. Conclusions: Hepatotoxic anti-TB drugs may be safely used in the patients with chronic liver disease including compensated cirrhosis if number of hepatotoxic drugs used is adjusted appropriately. [ABSTRACT FROM AUTHOR]

Summary: Objective:: Tuberculosis (TB) is an important opportunistic infection in HIV patients. Immune responses to Mycobacterium tuberculosis in HIV/TB patients were evaluated. Methods:: Fifteen patients with HIV/TB, ten with HIV, four with TB, and five controls were enrolled. Peripheral blood mononuclear cells were isolated and stimulated with mycobacterial antigen (PPD). Interferon (IFN)-γ and TNF-α in culture supernatants were measured by ELISA. Results:: IFN-γ and TNF-α production after PPD stimulation was markedly decreased in HIV patients, but not in HIV/TB patients. In HIV patients with a CD4 cell count of less than 200/mm3, IFN-γ and TNF-α production after PPD stimulation was higher in HIV/TB patients than in HIV patients. Cytokine responses to M. tuberculosis reconstituted after highly active antiretroviral therapy (HAART) and were prominent in HIV/TB patients. Conclusions:: Cytokine responses to M. tuberculosis were retained in HIV-infected patients with tuberculosis, even in patients with a CD4 cell count of less than 200/mm3, and reconstituted after HAART. [Copyright &y& Elsevier]

Gram-positive bacteria are frequently resistant to empirical beta‐lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130–14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366–11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059–0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218–0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer. [ABSTRACT FROM AUTHOR]

We report a case of a 25-year-old Caucasian female with a septic thrombosis in the inferior vena cava (IVC) which contained a toothpick. She was admitted with fever and abdominal pain for 2 weeks. Computed tomography scan showed thrombus with air density in the suprarenal IVC. However, there was no evidence of duodenocaval fistula. Because of the patient''s reluctance for surgery, endovascular therapy was tried. A partially-deployed nitinol stent was used as a filter, and aspiration thrombectomy was performed. Unexpectedly, a toothpick was retrieved within the stent. Anticoagulants and antibiotics were administered. A follow-up computed tomography after 2 months showed total resolution of the residual thrombus. [ABSTRACT FROM AUTHOR]

• The positivity rates of culture in tuberculous spondylitis were 69.0-85.3%. • The culture positivity rates were different according to biopsy methods and sites. • Targeting paraspinal tissues during needle biopsy might be the best method. We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS. We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues. During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13–11.99, P = 0.030). We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0–85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries. This phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged ≥50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23. The most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F). Administration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years. [ABSTRACT FROM AUTHOR]

• COVID-19 can deteriorate at the 2nd week of illness despite decreasing viral loads. • We analyzed PBMCs of severe or mild COVID-19 cases at the 1st and 3rd week of illness. • Cellular responses were not different between two groups at the 1st week of illness. • Higher T-cell proliferation, activation, and cytotoxicity was noted in severe cases at the 3rd week. • Aberrant hyperactivation of cytotoxic T-cell may contribute to severe COVID-19 pneumonia. We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8+ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group. Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19. [ABSTRACT FROM AUTHOR]

• A measles outbreak is occurring in South Korea despite high vaccine coverage. • Contact-adjusted immunity against measles is currently at 92%, increased from 86% in 2014. • There might be an option for catch-up campaigns to achieve herd immunity. • This is the first study to use contact patterns for understanding infectious disease outbreaks in South Korea. Measles has been reemerging in South Korea since December 2018 resulting in 185 cases by September 2019. We calculated contact-adjusted immunity levels against measles in South Korea using national seroprevalence data in 2014, vaccination uptake rates, and an age-specific contact matrix. We further explored options to achieve a contact-adjusted immunity level of 93% for herd immunity. The assessed contact-adjusted immunity level has increased from 86% in 2014 to 92% in 2018. Herd immunity could be achieved with immunizing 50% of susceptibles among birth cohorts 1999–2003 in 2018. Contact-adjusted immunity levels against measles have increased recently in South Korea, although they might not yet be high enough to guarantee herd immunity. [ABSTRACT FROM AUTHOR]

Background: Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults.Methods: This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter Reed Army Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18-50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT02670187) and is completed.Findings: Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five [20%] with 0·67 mg, 11 [44%] with 2 mg, and seven [28%] with 6 mg), and malaise or fatigue (five [20%] with 0·67 mg, seven [28%] with 2 mg, and two [8%] with 6 mg). The most common local solicited symptoms were administration site pain (23 [92%] with all three doses) and tenderness (21 [84%] with all three doses). Most solicited symptoms were reported as mild (19 [76%] with 0·67 mg, 20 [80%] with 2 mg, and 17 [68%] with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg group, three in the 2 mg group, and seven in the 6 mg group). Of these 15 increases, five (33%) were deemed possibly related to study treatment (one in the 2 mg group and four in the 6 mg group). Seroconversion measured by S1-ELISA occurred in 59 (86%) of 69 participants and 61 (94%) of 65 participants after two and three vaccinations, respectively. Neutralising antibodies were detected in 34 (50%) of 68 participants. T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. There were no differences in immune responses between dose groups after 6 weeks. At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively.Interpretation: The GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus.Funding: US Department of the Army and GeneOne Life Science. [ABSTRACT FROM AUTHOR]

• GC1109 is a novel recombinant protective antigen anthrax vaccine. • We evaluate the immunogenicity and safety of GC1109 in healthy adult volunteers. • Participants were randomized to three doses of GC1109 groups or placebo group. • GC1109 was immunogenic after three doses of intramuscular administration. • Although vaccine-related adverse events were frequent, most of them were mild. The demand on effective and safe anthrax vaccine is increasing as a part of the preparedness for possible bioterrorism in the future. We performed a randomized, single-blind, placebo controlled phase II clinical study to evaluate the immunogenicity and safety of a novel recombinant protective antigen (rPA) anthrax vaccine, GC1109, in healthy adult volunteers. Participants were randomized to experiment groups (0.3 mL, 0.5 mL, and 1.0 mL of GC1109) or placebo group (normal saline 0.5 mL) in 2:2:2:1 ratio. They received respective vaccines intramuscularly at 0, 4 and 8 weeks. Immunogenicity was evaluated by seroconversion rate and geometric mean titer (GMT) of lethal toxin neutralizing assay (TNA) and anti-PA IgG by ELISA. Safety was assessed by laboratory tests, and solicited and unsolicited adverse events on diary cards. 30, 29, 30 participants were randomized to 0.3, 0.5, and 1.0 mL of GC1109 groups, respectively, while 15 to placebo group. 92 participants received all three doses. In per-protocol analysis, TNA GMTs at week 12 were 296.5, 285.2, and 433.2 in the three groups, respectively. Seroconversion rates measured by ELISA were 100% at week 12 in the three groups. Local and systemic vaccine-related adverse events were frequent; however, most of them were mild, and no serious events were observed. A new rPA anthrax vaccine GC1109 was immunogenic after three doses of intramuscular administration, and was well-tolerated. [ABSTRACT FROM AUTHOR]

• The empirical use of broad-spectrum antifungal agents in prolonged febrile neutropenia during induction chemotherapy for acute myelogenous leukaemia should be re-evaluated in the era of antimould prophylaxis. • There were no significant differences in clinical outcomes between the empirical and pre-emptive groups, although the incidence of probable or proven invasive fungal infection (IFI) tended to be lower in the empirical group than in the pre-emptive group. • In the current era of antimould prophylaxis, broad-spectrum antifungal therapy in patients receiving antimold prophylaxis may be deferred until clinical or mycological evidence of IFI is obtained. This study compared clinical outcomes in patients with acute myelogenous leukaemia (AML) who developed prolonged (≥4 days) febrile neutropenia (FN) and received either empirical or pre-emptive antimould prophylaxis in order to evaluate the need for routine empirical antifungal therapy. This retrospective study reviewed adult patients (aged ≥18 years) with AML who developed prolonged FN and received antimould prophylaxis during induction or re-induction chemotherapy at a single centre between September 2016 and December 2020. Patients were categorized into pre-emptive or empirical groups based on whether or not there was clinical evidence of invasive fungal infection (IFI) at the start of antifungal treatment, respectively. Clinical outcomes were compared between the two groups after propensity score matching (PSM). In total, 229 chemotherapy episodes (36 and 193 in the empirical and pre-emptive groups, respectively) were analysed. In the pre-emptive group, broad-spectrum antifungal therapy was administered in 45 (23.3%) episodes. After 1:3 PSM, there were no significant differences between the empirical and pre-emptive groups in terms of the incidence of proven or probable IFI [0/36 (0%) vs 5/97 (5.2%); P =0.323], all-cause mortality [3/36 (8.3%) vs 4/97 (4.1%); P =0.388] and IFI-related mortality [0/36 (0.0%) vs 1/45 (2.2%); P =0.556]. The differences in clinical outcomes between empirical and pre-emptive antifungal therapy in patients with AML who received antimould prophylaxis were not significant. Therefore, broad-spectrum antifungal therapy in patients receiving antimould prophylaxis may be delayed until there is clear evidence of IFI. [ABSTRACT FROM AUTHOR]

The protective efficacy of human sera from vaccinated individuals with a new recombinant protective antigen anthrax vaccine (GC1109) against lethal spore challenge was evaluated in a mouse model. Eighteen human sera were selected from the vaccinated individuals based on their toxin neutralizing assay (TNA) titer (ED 50 of 55 to 668). The selected sera were diluted and passively transferred to A/J mice and the mice were subsequently challenged with 100 × LD 50 of Bacillus anthracis Sterne spores. The correlation between the survival rate of passively immunized mice and the TNA ED 50 of transferred sera was presented (r = 0.873, P-value < 0.001). The estimated TNA titer for 50% survival rate against lethal challenge was 197 (95% confidence interval of 149 and 260). The result suggest that GC1109 is protective against exposure to B. anthracis and the TNA titer of vaccinated serum can be an indicator for protective efficacy. [ABSTRACT FROM AUTHOR]

Rapid identification of the microorganisms in patients with bacteremia may be useful in clinical practice. We evaluated the impact of the multiplex polymerase chain reaction (PCR) on appropriate antibiotic use for patients with gram-positive cocci cluster (GPCC) bacteremia. We divided the GPCC bacteremia cases into a pre-PCR group (2010–2011) and a post-PCR group (2012–2013). A total 664 cases were included in the pre-PCR group; and 570, in the post-PCR group. In methicillin-susceptible Staphylococcus aureus (MSSA) cases, optimal antibiotics were administered earlier in the post-PCR group (77.4 h versus 42.6 h, P = 0.035). Although the proportions of glycopeptide exposure did not differ (54.7% versus 56.7%, P = 0.799), the duration of exposure decreased (69.6 h versus 30.7 h, P = 0.004). In methicillin-resistant S. aureus cases, the time to optimal antibiotics administration did not differ (45.4 h versus 43.7 h, P = 0.275). Multiplex PCR test significantly improved the early initiation of optimal antibiotics in MSSA bacteremia and reduced the unnecessary glycopeptide exposure. [ABSTRACT FROM AUTHOR]

Background Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. The detection of MERS-CoV sub-genomic mRNAs indicates that the virus is replicative. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens. Methods Upper and lower respiratory samples were obtained from 17 MERS-CoV-infected patients. MERS-CoV sub-genomic mRNA was detected by reverse transcription PCR (RT-PCR) and MERS-CoV genomic RNA by real-time RT-PCR. Results In sputum and transtracheal aspirate, sub-genomic mRNA was detected for up to 4 weeks after symptoms developed, which correlated with the detection of genomic RNA. In oropharyngeal and nasopharyngeal swab specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate. Conclusions These findings suggest that MERS-CoV does not replicate well in the upper respiratory tract. [ABSTRACT FROM AUTHOR]

A randomised controlled trial showed that rapid phenotypic antibiotic susceptibility testing (AST) with antimicrobial stewardship programme (ASP) increases the proportion of haematological patients with bacteraemia receiving optimal targeted therapy within 72 h of blood culture collection. This post-hoc analysis aimed to evaluate the effects of rapid phenotypic AST intervention in haematological patients at high risk of a poor outcome from bacteraemia. Haematological patients with bacteraemia (n = 116) were assigned randomly to a conventional AST group or a rapid AST group. The two outcome measures were the proportion of patients receiving optimal targeted therapy at 72 h post blood culture collection and the time to optimal targeted therapy; subgroup analysis was conducted based on baseline demographics (age, sex) and prognostic (Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score, appropriateness of empirical antibiotic therapy and multidrug-resistant organism) indicators. The interaction effect between the intervention and subgroup factors was examined using regression model analysis. Age, sex, Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score and appropriateness of empirical antibiotic therapy had no significant interaction effects on the proportion of patients receiving optimal targeted therapy (P = 0.129–0.826). However, infection by a multidrug-resistant organism did have a significant interaction effect (P = 0.042). Regarding time to optimal targeted therapy, there were no significant interaction effects between the intervention and subgroup factors (P = 0.156–0.848). In conclusion, rapid phenotypic AST with ASP intervention may accelerate early optimal targeted antimicrobial treatment of haematological patients, even those in high-risk subgroups with bacteraemia. [ABSTRACT FROM AUTHOR]

Highlights: [•] A new cell culture-derived smallpox vaccine (CJ-50300) was evaluated in healthy vaccinia-experienced adults. [•] Cutaneous “take” reactions were observed in 95.0% of CJ-50300 vaccinees. [•] The seroconversion rate in CJ-50300 vaccinees was 88.5%. [•] No serious adverse reactions were observed. [•] CJ-50300 can be used safely and effectively in healthy vaccinia-experienced adults. [Copyright &y& Elsevier]

Abstract: Nontuberculous mycobacteria (NTM) are classified into 2 categories: slow-growing mycobacteria (SGM) and rapid-growing mycobacteria (RGM), based on interval to colony formation by subculture on solid media. However, little is known about the growth rate of NTM in liquid broth media. We evaluated the differences in time to growth detection (TGD) of RGM and SGM in liquid broth media according to acid-fast stain. Among the 696 NTM isolates, 201 were RGM and 495 were SGM. In acid-fast bacilli (AFB)–negative specimens, the mean TGD was 133 h for RGM and 269 h for SGM (P < 0.001). In AFB-positive specimens, the mean TGD was 112 ± 37 h for RGM and 155 ± 125 h for SGM (P = 0.063). In the AFB-negative group, a cut-off value of 6 days was most effective for distinguishing SGM from RGM; however, in the AFB-positive group, an appropriate cut-off value was hard to define with TGD only. [Copyright &y& Elsevier]

Abstract: A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous “take” reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 99.2% (122/123), and 90.8% (109/120), respectively, and these rates did not differ significantly between the conventional-dose and the low-dose CJ-50300 (1.0×108 and 1.0×107 plaque-forming units/mL, respectively) (P >0.05 for each). No serious adverse reaction was observed. However, one case of possible generalized vaccinia occurred in the conventionally dosed group [ClinicalTrials.gov Identifier: NCT00607243]. [ABSTRACT FROM AUTHOR]

Abstract: Invasive candidiasis has emerged as an important nosocomial infection, especially in critically ill patients. The incidence of candidaemia in Intensive Care Units (ICUs) is 5- to 10-fold higher than in the entire hospital and the crude mortality rate of patients with candidaemia is between 35% and 60%. Candida albicans remains the predominant cause of invasive candidiasis in ICUs, followed by Candida tropicalis, Candida glabrata and Candida parapsilosis. Invasive isolates of Candida spp. remain highly susceptible to fluconazole (>90% susceptible), although among Asia-Pacific countries the susceptibility rate of C. glabrata to fluconazole varies widely from 22% to 72%. Early diagnosis and prompt initiation of antifungal therapy are crucial for the effective treatment of invasive candidiasis. However, invasive candidiasis is difficult to diagnose owing to its non-specific clinical features, and delayed therapy is a major contributor to poor outcomes. Combining clinical risk factors with Candida colonisation parameters appears promising for guiding early interventions. Because of considerable regional variability, local epidemiological knowledge is critical in the effective management of invasive candidiasis among ICU patients in Asia-Pacific. [Copyright &y& Elsevier]

Abstract: The whole-blood interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON-TB Gold [QFT-G]; Cellestis, Carnegie, Australia) has been studied mainly for diagnosing active pulmonary tuberculosis (TB) or latent TB. We prospectively evaluated its diagnostic usefulness in patients suspected with extrapulmonary TB (EP-TB). Of the 100 adult patients with suspected EP-TB, 43 were classified as “confirmed” EP-TB and 5 as “probable” EP-TB. Of the 48 with EP-TB, 27 (56%) were diagnosed with TB lymphadenitis and 11 (17%) with skeletal TB. The overall sensitivity and specificity of the assay were 69% (95% confidence interval [CI95], 53–81%) and 82% (CI95, 69–91%), respectively. Among 44 patients presented with cervical lymphadenopathy, the QFT-G assay showed 86% (CI95, 64–97%) sensitivity and 87% (CI95, 66–97%) specificity, whereas in 28 with skeletal involvement, the sensitivity and specificity of the assay were 45% (CI95, 17–77%) and 81% (CI95, 54–96%), respectively. These suboptimal diagnostic performances suggest that the QFT-G assay alone is not sufficient for the diagnosis of EP-TB. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to investigate the kinetics of humoral and cell-mediated immune responses to a new cell culture-derived smallpox vaccine (CJ-50300, CJ Corporation, South Korea) in 18 vaccinia-naïve volunteers. All subjects achieved positive humoral immune responses (plaque reduction neutralizing antibody assay) 28 days after vaccination, and cell-mediated immune responses (ELISPOT assay) 14 days after vaccination. Humoral immune responses increased up to 28 days after vaccination and were maintained up to 56 days after vaccination. In contrast, cell-mediated immune responses increased up to 14 days after vaccination and steadily decreased to 56 days after vaccination [Clinical Trial No. NCT 00336635]. [Copyright &y& Elsevier]

Abstract: To assess the effect of liver dysfunction on the production of C-reactive protein (CRP), CRP levels were evaluated in patients with Escherichia coli bacteremia with or without liver cirrhosis (LC). Thirty patients of each kind were selected as case and control groups, respectively. A matched control of 30 LC patients without acute infection was also included. In the patients with E. coli bacteremia, median CRP was 6.2 mg/dL (range 0.2–22.1) in the LC patients and 14.6 mg/dL (range 5.8–39.6) in the patients without liver dysfunction (P < 0.001). In the advanced LC patients in Child-Pugh class C, median CRP was 5.0 mg/dL (range 0.2–12.1) in patients with E. coli bacteremia and 0.5 mg/dL (range 0.1–1.2) in patients without acute infection (P < 0.001). Our data suggest that, although CRP levels are reduced in response to acute infection, production is nevertheless maintained even in patients with advanced liver dysfunction. [Copyright &y& Elsevier]

Summary: Objectives: This study was performed to determine the incidence of herpes zoster and seroprevalence of varicella-zoster virus (VZV) in young adults of South Korea, where VZV seroprevalence remains relatively high. Methods: In South Korea, military service is compulsory for all healthy young men and hence those in military service might provide a reflection of the general population. The computerized database of the Armed Forces Medical Command was examined to identify the number of reported herpes zoster cases. In order to evaluate VZV seroprevalence, serum samples were obtained from randomly selected subjects among those who had been admitted to the Armed Forces Capital Hospital. Results: A total of 705 cases of herpes zoster were reported between June 2004 and May 2005. The annual incidence rate of herpes zoster was 141 (95% CI 131.0–151.8) per 100000 population. A total of 192 subjects were enrolled for the analysis of VZV seroprevalence. All subjects were male and their median age was 21 (range 19–24) years. The overall anti-VZV IgG seropositivity prevalence was 92.7% (178/192, 95% CI 88.0–95.7%). Conclusion: We have described a population-based study of the epidemiology of VZV infections in the military personnel of South Korea. [Copyright &y& Elsevier]

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonosis that causes death in 35·7% of cases. As of Feb 28, 2018, 2182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide, with most being reported in Saudi Arabia (1807 cases with 705 deaths). MERS-CoV features prominently in the WHO blueprint list of priority pathogens that threaten global health security. Although primary transmission of MERS-CoV to human beings is linked to exposure to dromedary camels (Camelus dromedarius), the exact mode by which MERS-CoV infection is acquired remains undefined. Up to 50% of MERS-CoV cases in Saudi Arabia have been classified as secondary, occurring from human-to-human transmission through contact with asymptomatic or symptomatic individuals infected with MERS-CoV. Hospital outbreaks of MERS-CoV are a hallmark of MERS-CoV infection. The clinical features associated with MERS-CoV infection are not MERS-specific and are similar to other respiratory tract infections. Thus, the diagnosis of MERS can easily be missed, unless the doctor or health-care worker has a high degree of clinical awareness and the patient undergoes specific testing for MERS-CoV. The largest outbreak of MERS-CoV outside the Arabian Peninsula occurred in South Korea in May, 2015, resulting in 186 cases with 38 deaths. This outbreak was caused by a traveller with undiagnosed MERS-CoV infection who became ill after returning to Seoul from a trip to the Middle East. The traveller visited several health facilities in South Korea, transmitting the virus to many other individuals long before a diagnosis was made. With 10 million pilgrims visiting Saudi Arabia each year from 182 countries, watchful surveillance by public health systems, and a high degree of clinical awareness of the possibility of MERS-CoV infection is essential. In this Review, we provide a comprehensive update and synthesis of the latest available data on the epidemiology, determinants, and risk factors of primary, household, and nosocomial transmission of MERS-CoV, and suggest measures to reduce risk of transmission. [ABSTRACT FROM AUTHOR]