Background: Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. Objectives: The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. Methods: Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. Results: Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. Conclusions These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.

Background: Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. Objectives: The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. Methods: Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. Results: Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. Conclusions These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.

BACKGROUND/AIMS: Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is a major bloodstream infection with a high mortality rate. Identification of factors associated with early mortality in MRSAB patients would be useful for predicting prognosis and developing new therapeutic options. METHODS: A prospective cohort of MRSAB patients was examined between August 2008 and June 2011. Early and late mortality was defined as death within 2 and 28 days of blood culture, respectively. The clinical and microbiological characteristics in the early and late mortality and survival groups were compared. Risk factors associated with severe sepsis or septic shock were also investigated. RESULTS: A total of 385 adult MRSAB patients whose S. aureus isolates were available were enrolled; of these patients, 25 patients (6.5%) and 50 (13%) died early and late, respectively. Compared with both the late-mortality group and the survival group, severe sepsis or septic shock was a statistically significant independent risk factor associated with early mortality. Rapidly or ultimately fatal McCabe and Jackson classification (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI], 1.25 to 3.02) and pneumonia (aOR, 2.04; 95% CI, 1.03 to 4.02) were independently associated with severe sepsis or septic shock. A vancomycin minimum inhibitory concentration (MIC) ≥ 1.5 μg/mL was associated with a reduced incidence of severe sepsis or septic shock (aOR, 0.53; 95% CI, 0.34 to 0.84). CONCLUSIONS: Severity of illness seems to be the most important risk factor associated with early mortality in MRSAB. Although vancomycin MIC was not independently associated with early mortality, reduced vancomycin susceptibility appears to be linked to reduced disease severity.
Adult ; Bacteremia* ; Classification ; Cohort Studies ; Humans ; Incidence ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Microbial Sensitivity Tests ; Mortality* ; Odds Ratio ; Pneumonia ; Prognosis ; Prospective Studies ; Risk Factors ; Sepsis ; Shock, Septic ; Vancomycin

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.
Adult ; Bronchoalveolar Lavage Fluid* ; Bronchoalveolar Lavage* ; Chungcheongnam-do ; Diabetes Mellitus ; Drug-Related Side Effects and Adverse Reactions ; Glomerular Filtration Rate ; Humans ; Korea ; Lymphocyte Count ; Lymphocytes* ; Medical Records ; Multivariate Analysis ; Odds Ratio ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia* ; Risk Factors* ; Salvage Therapy ; Seoul ; Treatment Failure

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.
Adult ; Bronchoalveolar Lavage Fluid* ; Bronchoalveolar Lavage* ; Chungcheongnam-do ; Diabetes Mellitus ; Drug-Related Side Effects and Adverse Reactions ; Glomerular Filtration Rate ; Humans ; Korea ; Lymphocyte Count ; Lymphocytes* ; Medical Records ; Multivariate Analysis ; Odds Ratio ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia* ; Risk Factors* ; Salvage Therapy ; Seoul ; Treatment Failure

Salmonella is an intracellular pathogen with a cellular infection mechanism similar to that of Brucella, making it a suitable choice for use in an anti-Brucella immune boost system. This study explores the efficacy of a Salmonella Typhimurium delivery-based combination vaccine for four heterologous Brucella antigens (Brucella lumazine synthase, proline racemase subunit A, outer-membrane protein 19, and Cu/Zn superoxide dismutase) targeting brucellosis in goats. We inoculated the attenuated Salmonella delivery-based vaccine combination subcutaneously at two different inoculation levels; 5 × 10⁹ colony-forming unit (CFU)/mL (Group B) and 5 × 10¹⁰ CFU/mL (Group C) and challenged the inoculations with virulent Brucella abortus at 6 weeks post-immunization. Serum immunoglobulin G titers against individual antigens in Salmonella immunized goats (Group C) were significantly higher than those of the non-immunized goats (Group A) at 3 and 6 weeks after vaccination. Upon antigenic stimulation, interferon-γ from peripheral blood mononuclear cells was significantly elevated in Groups B and C compared to that in Group A. The immunized goats had a significantly higher level of protection as demonstrated by the low bacterial loads in most tissues from the goats challenged with B. abortus. Relative real-time polymerase chain reaction results revealed that the expression of Brucella antigens was lower in spleen, kidney, and lung of immunized goats than of non-immunized animals. Also, treatment with our combination vaccine ameliorated histopathological lesions induced by the Brucella infection. Overall, the Salmonella Typhimurium delivery-based combination vaccine was effective in delivering immunogenic Brucella proteins, making it potentially useful in protecting livestock from brucellosis.
Animals ; Bacterial Load ; Brucella abortus ; Brucella Vaccine ; Brucella ; Brucellosis ; Goats ; Immunoglobulin G ; Kidney ; Livestock ; Lung ; Proline ; Real-Time Polymerase Chain Reaction ; Salmonella typhimurium ; Salmonella ; Spleen ; Stem Cells ; Superoxides ; Vaccination

PURPOSE: The current live attenuated rabies vaccine must be replaced with a safer vaccine based on the ERAGS strain to prevent rabies in South Korea. We evaluated the safety and immunogenicity of a new strain in dogs and cattle. MATERIALS AND METHODS: The ERAGS strain, featuring two mutations altering two amino acids in a glycoprotein of rabies virus, was propagated in NG108-15 cells. We lyophilized the virus in the presence of two different stabilizers to evaluate the utilities of such preparations as novel rabies vaccines for animals. To explore safety and immunogenicity, dogs and cattle were inoculated with the vaccine at various doses via different routes and observed daily for 8 weeks post-inoculation (WPI). Immunogenicity was evaluated using a fluorescent antibody virus neutralization test or enzyme-linked immunosorbent assay. RESULTS: The two different stabilizers did not differ greatly in terms of maintenance of virus viability in accelerated stability testing. No clinical signs of rabies developed in dogs or cattle inoculated with the vaccines (10(7.0) FAID₅₀/mL). Dogs and cattle inoculated intramuscularly with 10(5.0) FAID₅₀/mL exhibited virus neutralization assay titers of 4.6 IU/mL and 1.5 to 0.87 IU/mL at 4 WPI, respectively. All control animals remained rabies virus–seronegative throughout, confirming that no contact transmission occurred between vaccinated and control animals. CONCLUSION: Our findings indicate that the new rabies vaccine is safe and immunogenic in dogs and cattle.
Amino Acids ; Animals ; Cattle* ; Dogs* ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; Korea ; Microbial Viability ; Neutralization Tests ; Rabies Vaccines* ; Rabies virus ; Rabies* ; Vaccines

BACKGROUND/AIMS: Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS: We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS: The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS: The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.
Cytomegalovirus* ; Ganciclovir ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells* ; Humans ; Incidence ; Kidney Transplantation ; Kidney* ; Prospective Studies ; Retinitis ; Tissue Donors ; Transplant Recipients*

BACKGROUND: Mucormycosis is an uncommon and life-threatening fungal infection. The clinical predictors of outcome were evaluated in patients with invasive mucormycosis. MATERIALS AND METHODS: We retrospectively reviewed histologically proven cases of invasive mucormycosis in our institution from 1996 to 2012. RESULTS: A total of 64 patients were analyzed. The median age was 59 years (interquartile range [IQR], 50-67), and 32 patients (50%) were male. The most common underlying diseases were diabetes mellitus (67%), hematologic malignancy (22%), and solid cancer (19%). The most common infection sites were the rhino-orbito-cerebral area (56%) and the lungs (31%). The 180-day all-cause mortality was 33%. Disseminated infection was associated with increased mortality (hazard ratio [HR]: 169.74, 95% confidence interval [CI]: 6.41 to 4492.64; P = 0.002). Pulmonary infection (HR: 0.08, 95% CI: 0.01 to 0.66; P = 0.02) and complete surgical removal of infected tissue (HR: 0.12, 95% CI: 0.02 to 0.64; P = 0.01) were associated with decreased mortality. CONCLUSIONS: These results suggest that patients with mucormycosis had a lower risk of mortality if they developed a pulmonary infection, rather than a disseminated infection and with complete debridement of infected tissue.
Debridement ; Diabetes Mellitus ; Hematologic Neoplasms ; Humans ; Lung ; Male ; Mucormycosis ; Retrospective Studies ; Risk Factors

Listeria monocytogenes is a facultative anaerobic gram positive rod bacteria that is wide spread in the natural environment and found in soil, water, decaying vegetation, and as part of the fecal flora of many mammals. It is also a common cause for meningoencephalitis and bacteremia in at-risk groups including neonates, pregnant women, elderly persons, and immunocompromised patients. However, pneumonia with pleuritis is a very rare manifestation of L. monocytogenes. We report a case of pneumonia with pleural effusion caused by L. monocytogenes as isolated from the blood culture of a patient diagnosed with acute lymphoblastic leukemia resulting from induction chemotherapy. The patient recovered after the introduction of therapeutic thoracentesis and administration of intravenous ampicillin (2 g q 6 hr) plus gentamicin (1.7 mg/kg q 8 hr) over a two week period. This case demonstrated that L. monocytogenesis infection should be a consideration in the differential diagnosis of pneumonia and pleuritis in leukemic patients.
Aged ; Ampicillin ; Bacteremia ; Bacteria ; Diagnosis, Differential ; Female ; Gentamicins ; Humans ; Immunocompromised Host ; Induction Chemotherapy ; Infant, Newborn ; Listeria ; Listeria monocytogenes ; Mammals ; Meningoencephalitis ; Pleural Effusion ; Pleurisy ; Pneumonia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Pregnant Women ; Soil