Immunogenicity of a bivalent killed thimerosal-free oral cholera vaccine, Euvichol, in an animal model

PURPOSE: An oral cholera vaccine (OCV), Euvichol, with thimerosal (TM) as preservative, was prequalified by the World Health Organization (WHO) in 2015. In recent years, public health services and regulatory bodies recommended to eliminate TM in vaccines due to theoretical safety concerns. In this study, we examined whether TM-free Euvichol induces comparable immunogenicity to its TM-containing formulation in animal model. MATERIALS AND METHODS: To evaluate and compare the immunogenicity of the two variations of OCV, mice were immunized with TM-free or TM-containing Euvichol twice at 2-week interval by intranasal or oral route. One week after the last immunization, mice were challenged with Vibrio cholerae O1 and daily monitored to examine the protective immunity against cholera infection. In addition, serum samples were obtained from mice to measure vibriocidal activity and vaccine-specific IgG, IgM, and IgA antibodies using vibriocidal assay and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant difference in immunogenicity, including vibriocidal activity and vaccine-specific IgG, IgM, and IgA in serum, was observed between mice groups administered with TM-free and -containing Euvichol, regardless of immunization route. However, intranasally immunized mice elicited higher levels of serum antibodies than those immunized via oral route. Moreover, intranasal immunization completely protected mice against V. cholerae challenge but not oral immunization. There was no significant difference in protection between two Euvichol variations. CONCLUSION: These results suggested that TM-free Euvichol could provide comparable immunogenicity to the WHO prequalified Euvichol containing TM as it was later confirmed in a clinical study. The pulmonary mouse cholera model can be considered useful to examine in vivo the potency of OCVs.

Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea

The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).

Erratum: Addition of Author's Affiliated Institute and Correction of the Author's Name. Corrected: Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea

We found errors in our published article.

Erratum: Addition of Author's Affiliated Institute and Correction of the Author's Name. Corrected: Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea

We found errors in our published article.

Plasma, Tissue Thiobarbituric Acid Reactive Substance and Lymphocyte Oxidative DNA Damage in Mouse Fed Gamma Irradiated Diet

Food irradiation has been steadily increasing in many countries in line with increasing international trade and concerns about naturally occurring harmful contaminants in food. Although irradiation provides an excellent safeguard for the consumer by destroying almost 100% of harmful bacteria, it is necessary to ensure the safety of irradiated foods. This study was performed to investigate the effect of an irradiated diet on lipid peroxidation in the plasma, liver, small intestinal mucosa, and lymphocyte DNA damage in mice. Eight-week old ICR mice were assigned to two groups to receive either non-irradiated or irradiated (10 kGy) diets containing 20.38% fish powder and 6.06% sesame seeds for 4 weeks. The resulting changes in the degrees of lipid peroxidation were evaluated based on the level of plasma and liver thiobarbituric acid reactive substance (TBARS), transmission electron micrograph of jejunal mucosa, and free radical-induced oxidative DNA damage in lymphocytes, as measured by alkaline comet assay (single cell gel electrophoresis). The peroxide values of the gamma irradiated diet were measured every week, and the sample for comet assay was taken at the end of the four week experimental period. There was no significant difference in food efficiency ratio between the two groups. The peroxide values of the diet were immediately increased to 35.5% after gamma irradiation and kept on increasing during storage. After 4 weeks, no differences in tissue or plasma TBARS value were observed between the two groups, but epithelial cells of jejumum showed osmiophillic laminated membranous structures, considered as myelin figures,. The oxidative DNA damage expressed as tail moment (TM) increased 30% in the blood lymphocytes of the mice fed the irradiated diet. In conclusion, the comet assay sensitively detected differences in lymphocyte DNA damage after feeding with the irradiated diet for 4 weeks. However, in order to ensure the safety of irradiated foods, it would be more useful to conduct a long-term feeding regimen using an irradiated diet and examine the level of lipid peroxidation and the state of oxidative stress in a greater range of organs.

A Case of Narcolepsy Diagnosed by Multiple Sleep Latency Test

Narcolepsy is a serious, lifelong, disabling disorder characterized by a tetrad of symptoms including excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. We experienced a 14 year old boy with a narcolepsy diagnosed by typical clinical symptoms above mentioned and multiple sleep latency test. A brief review of the related literatures was also made.

A Case of Early Onset Cerebellar Ataxia with Retained Tendon Reflexes

Early onset cerebellar ataxia with retained tendon reflexes is clinical syndrome characterized by progressive cerebelar ataxia of unknown etiology with an onset within the first two decades. This disorder was distinguished from Friedreich's ataxia by the preservation of the tendon reflexes. We have experienced a case of early onset cerebellar ataxia with retained tendon reflexes which was diagnosed by clinical features, eletrophysiologic studies, and MRI scan. This 8 year-old male patient had suffered from gait ataxia with delayed growth and development since 3 years of age. A brief review of the related literatures was also made.

A Case of Early Onset Cerebellar Ataxia with Retained Tendon Reflexes

Early onset cerebellar ataxia with retained tendon reflexes is clinical syndrome characterized by progressive cerebelar ataxia of unknown etiology with an onset within the first two decades. This disorder was distinguished from Friedreich's ataxia by the preservation of the tendon reflexes. We have experienced a case of early onset cerebellar ataxia with retained tendon reflexes which was diagnosed by clinical features, eletrophysiologic studies, and MRI scan. This 8 year-old male patient had suffered from gait ataxia with delayed growth and development since 3 years of age. A brief review of the related literatures was also made.

A Case of Multicystic Encephalomalacia in a Liveborn Twin with a Stillborn Co-twin

Multicystic encephalomalacia is the condition defined anatomically by the presence of multiple cavities in the great part of both cerebral hemispheres. The most common cause of the condition was regarded as the circulatory disturbance during the perinatal period. Also, neonatal asphyxia was the most important cause of the circulatory disturbance. But we experienced a case of multicystic encephalomalacia in a liveborn twin with a stillborn co-twin without perinatal asphyxia. It seems likely that intrauterine disseminated intravascular coagualation owing to fetofetal transfer of thromboplastic material from the dead fetus through vascular shunts in a monochorionic placenta without neonatal asphyxia constitute the main cause of the neurologic complication in our patient. So we report with a brief review and its related literatures.

Clinical Study of the Risk Factors of Recurrence after the Antiepileptic Drug Discontinuation in Childhood Epilepsy

59 children seen from Jan. 1990 to Jun. 1994 with epilepsy were retrospectively reviewed to evaluate the tendency of recurrence and the risk factors after the antiepileptic drug discontinuation. The population consisted of 59 children who were seizure free for more than 2 years and followed up for more than 1 year after the discontinuation via department of pediatrics, Yonsei University, Wonju College of Medicine. We analyzed risk factors of recurrence(age of seizure onset, seizure frequency before treatment, interval from seizure onset to start of treatment, duration from neurologic disorders, and EEG done just before discontinuation) between non-recurrent group(43 patients) and recurrent group(16 patients). The results were as follows: 1) In 59 patients with epilepsy, 16(27.1%) patients showed recurrence after the discontinuation and 14(87.5%) patients of those were developed during taperring and within less than 1 year. The probability of recurrent seizure by Kaplan-Meier curve at 12 and 24 months after discontinuation are 23.7% and 33.6% respectively. 2) There were significant differences on seizure frequency before treatement, duration from start of treatment to control (9.5months vs 31.1months), and associated neurologic disorders(11.6% vs. 56.2%) between non-recurrent and recurrent group. 3) There were no significant differences on age at seizure onset(70.6 months vs. 58.5months), interval from seizure onset to start of treatment(9.5months vs. 6.6months), length of seizure free(49.7months vs 39.3months), abnormal EEG finding done just before withdrawal(23.2% vs. 25.0% ) between non-recurrent and recurrent group.

Intermittent Rhythmic Delta Activity(IRDA) in Children

BACKGROUND: Intermittent rhythmic delta activity (IRDA) is classified as a nonspecific abnormal EEG pattern. IRDA is clinically associated with alteration of consciousness, hydrocephalus, cerebral edema, deep midline lesions, subcortical lesions, and tumors of the posterior fossa and the third ventricle. Frontal IRDA(FIRDA) is usually seen in patients over age 15 years, whereas occipital IRDA(OIRDA) occurs mainly in children. We have investigated the clinical feature and significance of IRDA in children. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 36 children with IRDA of EEG concerning diagnosis, neurologic examination, classification of epilepsy, and CT & MRI findings. RESULTS: 1) The location of the IRDA was frontal(FIRDA) in 11 of 36(30.5%), occipital(OIRDA) in 20 of 36(55.6%) and mixed in 5 of 36(13.9%) patients. 2) Thirty of 36(83.3%) have epilepsy (including 1 each with MELAS and tuberous sclerosis), 4 of 36(11.1%) have migraine and 2 of 36(11.1%) patients have meningitis. 3) Sixteen of 30(53.3%) have partial or partial with secondary generalized seizure, 10 of 30(33.3%) have generalized seizure and 4 of 30(13.3%) patients with epilepsy have absence seizure. 4) Neuroimaging studies (CT or MRI scan) were performed in 27 cases. Among 27 cases of studies, 6 cases(22.2%) were abnormal including; two cases of infections, and each case of infarction, venous angioma, arachnoid cyst, cortical atrophy, and tuberous sclerosis, respectively. CONCLUSIONS: IRDA may be considered an epileptiform pattern in childhood and FIRDA is frequently seen in children than previous reports.

Clinical Use of Video-EEG Monitoring in Children

No abstract available.

A Case of Common Bile Duct Stone Treatment with Endoscopic Sphincterotomy

The cholelithiasis and common bile duct(CBD) stone are rare problems among children. Endoscopic retrograde cholangiopancretogram(ERCP) and endoscopic sphincterotomy are rarely commomly utilized in the treatment of children, primarily because there are fewer indications. ERCP is an established procedure for visualization of the biliary tract. Endoscopic sphincterotomy with stone extraction has been accepted as the treatment of choice for CBD stone removal in adults. However, the role and value of these procedures in children are not as clear. We experienced a case of CBD stone in 3-year-old boy, who suffered reccurent jaundice and abdominal pain. The boy was administrated and was diagnosed with a mild abnormal gallbldder on ultrasound. Laboratory data showed obstructive jaundice, so, an ERCP was performed and identified that the child had a distal CBD stone. An Endoscopic sphincterotomy was then performed. After the sphincterotomy, the stone passed the Ampulla of Vater spontaneously without the use of a Dormia basket or Forgathy catheter.

Granulocytic Sarcoma in the Cerebellum

Granulocytic sarcoma, a rare extramedullary solid tumor arising from early myeloid precursors, is capable of invading the meninges or the rain parenchyma. The tumor may occur during or after the onset of systemic myelogenous leukemia. On rare occasions, the tumor may evolve before the onset of systemic myelogenous leukemia. Children are affected more often than adults, but sex is not related. Although no definite target area of the brain can be demonstrated, there may be some predilection of the tumor for the posterior fossa. The authors report a case of 4-year-old-boy with granulocytic sarcoma occurring in the posterior fossa presenting with gait disturbance and torticollis. The patient was treated by surgical removal of the tumor, there by avoiding the potentially lethal complication of a posterior fassa mass. This rare case is reported together a review of the literature.

Diagnostic Significance of Red Cell Indices in Non-anemic Iron Deficiency and Iron Deficiency Anemia: Reevaluation with ROC Curve

To validate the diagnostic significance of red cell indices in non-anemic iron deficiency and iron deficiency anemia, complete blood count, serum iron, total iron binding capacity, and serum ferritin were measured in 208 middle school girls between 13 and 15 years of age. We used Reciever Operatin Characteristic (ROC) curve to compare the diagnostic significances of various red cell indices (MCV, MCH, MCHC, RDW). We also established the ideal cutoff values of red cell indices for the diagnosis of iron deficiency anemia. The results were as follows: 1) The prevalence of iron deficiency anemia and non-anemic iron deficiency were 4.8% and 11.1% respectively. 2) For the diagnosis of iron deficiency anemia, MCV had the highest diagnostic capacity, and MCH was the secondly useful one. 3) For the diagnosis of non-anemic iron deficiency. MCV had the highest diagnostic capacity, but the sensitivity and specificity of the 4 red cell indices(MCV, MCH, MCHC, RDW) were so low that they could not be used as screening or confirmative tests. 4) The sensitivity and specificity of MCV were 1 for the diagnosis of iron deficiency anemia(cutoff value: MCV=79 fl). In case of MCH, the sensitivity was. 1 and the specificity was 0.995 for the diagnosis of iron deficiency anemia(cutoff value: MCH=25pg). In case of MCHC, the sensitivity was 1 and the specificity was 0.69 for the diagnosis of iron deficiency anemia (cutoff value: MCH-33g/dl). In case of RDW, the sencitivity was 0.9 and the specificity was 0.96 for the diagnosis of iron deficiency anemia(cutoff value: RDW=13.5%). With above results, we could conclude that MCV and MCH were very useful screening tests for iron deficiency anemia and MCV could be used as a confirmative test of iron deficiency anemin.

Isolated Angiitis of the Cnetral Nervous System

Isolated angiitis of the central nervous system is a rare clinicopathologic entity characterized by vasculitis restricted to the vessels of central nervous system without other apparent systemic vasculitis. It manifests headache, higher cortical dysfunction. focal neurologic dysfunction and cranial nerve palsies. We experienced a case of isolated angiitis of the central nervous system in 6 year-old girl who was admitted to out unit because of headache, hemiparesis and altered consciousness. The laboratory test for blood, urine, and cerebrospinal fluid are all within normal ranges. There was no evidence of systemic vasculitis. The contrast enhanced brain CT scan showed low densities along the left cerebellar hemisphere and posterior aspect of temporal lobe without enhancement, and left lateral internal carotid angiogram showed poorly contrast filling along the territory of left posterior cerebral artery due to narrowing or ischemic changes of the vessels. Axial T2WI (TR/TE, 2190/80) of magnetic resonance imaging showed multiple scattered high signal intensities at left pons with cerebellar hemisphere and diffuse high signal intensity along the left occipital lobe with enlarged surrounding gyral patterns, and axial T1WI(TR/TE, 665/25) showed intense gyral pattern contrast enhancement along the left occipital lobe. Steroid was tried with apparent benefit. We report a case of isolated angiitis of central nervous system with review of literature.

A Case of Central Diabetes Insipidus Associated with Brachycephaly

Brachycephaly is a kind of craniosynostosis. Because of premature closure of the coronal suture, the skull is shorter in the anteroposterior diameter but is widened with a high vault and the occiput and forehead are flattened. Diabetes insipidus had been reported in oxycephaly. We have experienced a case of central diabetes insipidus associated with brachycephaly. A brief review of related literatures is included in this report.

2 cases of acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an acute inflammatory demyelinating disease of the central nervous system. It is thought to be an autoimmune mediated disorder which occurs usually after viral or bacterial infections, or after immunization. The clinical manifestations reflect sudden onset of the diffuse involvement of the brain, spinal cord and the meninges. We experienced two cases of acute disseminated encephalomyelitis. The diagnoses were made by history, neurologic examination, CSF analysis and brain MRI. The symptoms were improved with steroid treatment. A brief reveiw of literatures also was made.

Clinical observation of aseptic meningitis associated with mucocutaneous lymph node syndrome

Clinical observation was carried out for 147 patients with mucocutaneous lymph node syndrome (MCLS) who were admitted to the Department of Pediatrics, Wonju Christian Hospital during the period from June, 1983 to June, 1992. A spinal tap was performed on 114 of these patients and the following results were obtained. 1) The incidence of aseptic meningitis in patients with MCLS was 52.6%. (60 cases of the 114 cases who had spinal taps (52.6%).) 2) The predominent age group for aseptic meningitis was 6 months to 1 year of age (35%). 3) For the majority, the value of glucose and protein in the CSF were within normal limit or only mildly elevated. 4) The neurologic manifestations associated with aseptic meningitis in patients with MCLS were irritability (78.3%), vomiting (25.0%), nuchal rigidity (11.7%), convulsion (5.0%) and facial nerve palsy (1.7%) in that order.

Three cases of purpura fulminans

Purpura fulminans is one of rare consumptive coagulopathy in children. The most common predisposing conditions of purpura fulminans are infectious disease like streptococcal infection and chickenpox. This disease is characterized by ecchymotic lesions that are usually distributed symmetrically on the lower extremities and buttocks. These ecchymotic lesions undergo necrosis, unless there is effective treatment. We experienced 3 cases of purpura fulminans which improved almost completely after early heparin administration. In the case 1, a 12 month old girl, purpura fulminans developed during sepsis and gastroenteritis. In the case 2, a 4 month old boy, purpura fulminans developed during acute sepsis. We reported 3 cases with a brief review of related literature.