A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Clinical Outcomes of Nasolacrimal Probing and Silicone Intubation in Patients with Congenital Nasolacrimal Duct Obstruction

PURPOSE: To investigate the efficacy and factors affecting the success rates of nasolacrimal probing and silicone intubation (SI) in patients with congenital nasolacrimal duct obstruction (CNLDO). METHODS: We retrospectively reviewed the medical records of patients including 69 eyes of 59 patients who received probing and 61 eyes of 49 patients who received SI. In patients with probing, the age, sex, and history of conservative treatment were analyzed in the success and failure groups, and a success rate comparison was conducted by dividing these values into postnatal group 1 ( 12 months, the success rate of probing was lower than in patients 12 months.

The Correlation between Preoperative En Face Optical Coherence Tomography and Postoperative Visual Prognoses in Idiopathic Epiretinal Membranes

PURPOSE: To investigate the correlation between en face optical coherence tomography and improvements in the postoperative prognoses of idiopathic epiretinal membranes. METHODS: The medical records of 59 epiretinal membrane patients who had epiretinal membrane peeling between January 2005 and January 2016, and were followed up for > 12 months, were retrospectively reviewed. The preoperative en face images were divided into four sections involving three circular areas (6,000 µm diameter circle, 3,000 µm diameter circle, and 1,000 µm diameter circle) and one square (6,000 × 6,000 µm). The surface area where no epiretinal adhesion was present was quantified by measuring the number of black pixels using image-editing software (Adobe Photoshop CS6, Adobe Systems, San Jose, CA, USA). Then the correlations among the value of black pixels, preoperative and postoperative visual acuities, and central retinal thickness were analyzed. RESULTS: The best-corrected visual acuity (BCVA) was significantly increased after epiretinal membrane peeling (p < 0.001), and the central retinal thickness was significantly decreased (p < 0.001). As the number of black pixels in the circles and the square in the en-face images increased, the postoperative BCVA significantly increased (r = 0.645, p < 0.001; r = 0.590, p < 0.001, respectively). CONCLUSIONS: As the nonadhesive surfaces of the epiretinal membrane and the retina in preoperative en face images became wider, the increments of the BCVA after surgery were greater. Therefore, en face optical coherence tomography can be used to predict prognosis after epiretinal membrane peeling.

Direct Detection of Drug-Resistant Hepatitis B Virus in Serum Using a Dendron-Modified Microarray

BACKGROUND/AIMS: Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. METHODS: The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. RESULTS: The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. CONCLUSIONS: We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues.

The Clinical Manifestations and Differential Diagnosis of Tuberculosis Serpiginous-like Choroiditis and Serpiginous Choroiditis

PURPOSE: The purpose of this study is to make a distinction between tuberculous serpiginous-like choroiditis and serpiginous choroiditis, and compare their clinical manifestations. METHODS: We retrospectively reviewed thirty eight eyes of twenty-six patients who visited our institution and were diagnosed with serpiginous choroiditis from January 2005 to December 2014. The patients were divided into two groups, tuberculosis serpiginous- like choroiditis (Tb-SLC) and classic serpiginous choroiditis (classic SC), and were analyzed based on the treatment response, previous history of Bacillus Calmette–Guérin (BCG) vaccination, positive results of tuberculin skin test (TST), chest X-ray, anterior and fundus examination, and fluorescein angiography (FAG). RESULTS: Twenty seven eyes of eighteen patients were serpiginous choroiditis and eleven eyes of eight patients were tuberculosis serpiginous-like choroiditis. There were no significant differences in age, sex, or previous history of BCG vaccination between the two groups. The positive result of the tuberculin skin test and abnormality in the chest X-ray were shown to be significantly higher in the Tb-SLC group. Multi-focal lesions involving periphery observed in fundus examination and FAG were significantly higher in Tb-SLC. CONCLUSIONS: In tuberculosis endemic areas such as Korea, tuberculosis serpiginous-like choroiditis should be considered as a differential diagnosis when the patient is suspicious of serpiginous choroiditis. The understanding of various clinical manifestations of tuberculosis serpiginous-like choroiditis may derive accurate diagnosis and treatment, enhancing patient's prognosis.

The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.

The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.