A randomized, observer-blind, controlled phase III clinical trial assessing safety and immunological non-inferiority of Vi-diphtheria toxoid versus Vi-tetanus toxoid typhoid conjugate vaccine in healthy volunteers in eastern Nepal.

Typhoid remains one of the major serious health concerns for children in developing countries. With extremely drug-resistant cases emerging, preventative measures like sanitation and vaccination, including typhoid conjugate vaccines (TCV) remain the mainstay in its prevention and control. Different types of TCVs are being developed to meet the global demand. This report outlines the results from a study done to assess the immunogenicity and safety of Vi-Diphtheria toxoid (Vi-DT) TCV in Nepal. The study was a randomized, active-controlled, immunological non-inferiority and safety study. Eligible participants from Sunsari and Morang districts of eastern Nepal were randomized into 4 study groups (A-D) within 3 age strata (6 months to <2 years, 2 to <18 years, and 18 to 45 years). Groups A to C received a single dose (25 µg) of Vi-DT test vaccine from any of the 3 lots, while group D received the comparator, Typbar-TCV®, Vi-tetanus toxoid (Vi-TT) vaccine (25 µg) in 1:1:1:1 ratio and evaluated at 4 weeks postvaccination with 6 months follow-up. Amongst 400 randomized participants, anti-Vi-IgG seroconversion rates for all age strata in Vi-DT pooled groups (A+B+C) were 100.00% (97.5% CI 98.34-100.00) vs 98.99% (97.5% CI 93.99-99.85) in Vi-TT group (D) at 4 weeks. Comparable safety events were reported between the groups. Three serious adverse events (1 in Vi-DT; 2 in Vi-TT group) were reported during the 6 months follow-up, none being related to the investigational product. Thus, Vi-DT vaccine is safe, immunogenic, and immunologically non-inferior to Vi-TT when analyzed at 4 weeks postvaccination.

Cystinuria, an Atypical Presentation and Challenges of Establishing its Diagnosis in a Poor Resource Set Up.

Cystinuria is an autosomal recessive defect in re-absorptive transport of amino acids: cysteine, ornithine, arginine and lysine from renal proximal convoluted tubules leading to urinary excretion of these amino acids. The phenotypic manifestations are recurrent urolithiasis, hematuria, flank pain and frequent urinary tract infection. An eighteen years old boy, diagnosed case of cystinuria at the age of two years is presented in this case report highlighting the atypical presentation of recurrent infections with multiple organ involvement. The challenges in establishing the diagnosis and the role of simple biochemical tests in confirming the diagnosis in a poor resource setup is highlighted. Performance of simple biochemical tests in the urine sample of this patient was done for the utility of these tests for future diagnostic purpose in any suspected cases of cystinuria in our set up. Keywords: Case report; cystinuria; Nepal.

Profile of children with cerebral palsy at a tertiary hospital in eastern Nepal.

BACKGROUND: The clinical spectrum of Cerebral palsy (CP) can differ in various places depending upon knowledge of the people and resources for prevention, diagnosis and management. Although studied extensively in high-resource countries, adequate data related to CP from resource-constraint settings are lacking. This study aims to describe the profile of children with CP at a tertiary care center in eastern Nepal. METHODS: This was a hospital-based cross-sectional descriptive study done from 2017 to 2018. Children 6 months to 15 years who presented with CP were enrolled and their clinical details recorded and described. RESULTS: Amongst 110 children with CP, 74.54% were male. Majority (76.36%) were 5 years or below with the median age being 3(2.00-4.75) years. Children with spastic quadriplegia (44.44%) and Gross Motor Function Classification System level III (41.81%) were most common. Etiologically, perinatal factors (64.54%) like perinatal asphyxia (35.45%) and prematurity (20.90%) and postnatal infections (25.45%) were common. The common comorbidities were intellectual disability (71.81%) and epilepsy (66.36%). The main treatment modalities were: antiepileptics (59.09%) and centre-based physiotherapy sessions (35.45%). School education was provided in 23.07% with special education in 11.53%. CONCLUSIONS: This study describes the profile of CP at our centre in eastern Nepal. Predominance of perinatal complications and postnatal infections points towards the urgent need to further improve the perinatal and neonatal health care delivery system and practices.

Gestational age specific anthropometric postnatal percentile charts for neonates born at tertiary hospital in Eastern Nepal.

BACKGROUND AND OBJECTIVES: Birth weight, Head circumference (HC), and Length are important clinical indicators for evaluation of prenatal growth and identification of neonates requiring detail assessment and monitoring. Gestational age-specific percentile charts are essential tool for both obstetricians and pediatricians in their day to day practice. This study aimed to develop gestational age specific percentile chart of Birth weight, Length and HC for neonates. METHODS: In this Cross sectional observational study, HC, Birth weight and Length of live singleton neonates from 28 to 42 weeks of gestation fulfilling the inclusion criteria were measured over a period of one year. Mean, standard deviation, and percentiles values for different gestational age were calculated. Graphs were constructed using two way graph and Lowess smoothening method. RESULTS: Of total 2662 neonates, male: female ratio was 1.3:1 with maximum neonates in 40 weeks of gestation. The mean Birth weight, HC and Length was 2852.02 gm, 33.6 and 48.42 cm respectively. Overall males have more mean weight than females by 46.35gms. However, mean HC of male and female were similar 33.6 and 33.61 cm respectively and on average males were 0.27 cm longer compared to female. The mean Birth weight, HC and Length at 40 weeks was 3123.43gm (± 427.82), 34.249 cm (± 0.87) and 49.61 cm(± 1.85) respectively. The 10th, 50th and 90th percentile at 40 weeks for Birth weight being 2550gm, 3100gm and 3750gm respectively. The gestational age specific percentile chart and growth curve are appropriately placed in the manuscript. CONCLUSIONS: The percentile charts in this study may be used as reference for local population and similar data from various parts of the nation can provide a national reference curve for healthy neonates.

Serum procalcitonin in bacterial & non-bacterial meningitis in children.

BACKGROUND: Bacterial meningitis is a paediatric emergency with high mortality and morbidity requiring prompt diagnosis and treatment. Clinically, it is often difficult to differentiate between bacterial and non-bacterial meningitis. Several studies have demonstrated the raised values of serum procalcitonin (PCT) in bacterial infections including meningitis but without definite cut-off guidelines. Hence, this study was done to evaluate serum PCT as a marker to differentiate bacterial and non-bacterial meningitis in children and assess its efficacy. METHODS: It was a cross-sectional study done over a period of 5 months (Aug 2016-Dec 2016) in the department of Paediatrics, B P Koirala Institute of Health Sciences (BPKIHS). Fifty children aged 3 months to 15 years with suspected meningitis were enrolled and investigated with relevant investigations like complete blood counts, and cerebrospinal fluid (CSF) analysis along with serum PCT. Patients were classified into bacterial (22) and non-bacterial meningitis (28) according to clinical & CSF findings and data analysed using SPSS software. RESULTS: Serum PCT levels were significantly higher in bacterial meningitis group (median = 2.04 (1.2-3.18) ng/ml) compared with non-bacterial meningitis (median = 0.35 (0.18-0.35) ng/ml); p < 0.001. The sensitivity and specificity of serum PCT in diagnosis of bacterial meningitis at cut-off level of 0.5 ng/ml were 95.45% and 84.61% respectively. Procalcitonin showed maximum area under receiver operating characteristics (ROC) curve 0.991 (0.974-1.00) (p < 0.001) compared to total leukocyte count and CSF cytochemistry. CONCLUSION: Serum PCT has high sensitivity and specificity for early diagnosis of bacterial meningitis in children. Hence it can be a useful adjunct in differentiating bacterial and non-bacterial meningitis for prompt and better management of the children.

Prevalence of electrolyte disturbances in perinatal asphyxia: a prospective study.

BACKGROUND: Birth asphyxia is defined as the presence of hypoxia, hypercapnia, and acidosis leading the newborn to systemic disturbances probably electrolyte disturbance also. Knowledge of these electrolyte disturbances is very valuable as it can be an important parameter affecting perinatal morbidity, mortality and ongoing management. METHODS: Serum sodium, potassium and ionized calcium of asphyxiated term newborn were sent within one hour of birth as per the inclusion criteria. Statistical comparison of mean values of different electrolytes between different groups of perinatal asphyxia was performed by ANOVA test for parametric data and significant data were further analyzed using post hoc test. Bivariate analysis was done to determine the correlations between Apgar score at 5 min and serum electrolytes. Pearson test was used to calculate the correlation coefficient. Box plot was used to show the median and quartile between serum electrolytes and Apgar score at 5 min. RESULT: The mean values of sodium for mild, moderate and severe asphyxia were 135.52, 130.7 and 127.15 meq/l respectively. The values of potassium for mild, moderate and severe asphyxia were 4.96, 5.93 and 6.78 meq/l respectively. Similarly, the mean values of ionized calcium for mild, moderate and severe asphyxia were 1.07, 1.12 and 0.99 mmol/l respectively. The values of sodium and potassium among different severity of asphyxia were significantly different (p-value< 0.001). Significant positive correlation was found between serum sodium and Apgar score at 5 min. Significant negative correlation was present between serum potassium and Apgar score at 5 min. CONCLUSION: The degree of hyponatremia and hyperkalemia was directly proportional to the severity of birth asphyxia. So these electrolyte disturbances should always be kept in mind while managing cases of perinatal asphyxia and should be managed accordingly.

A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

BACKGROUND: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. CONCLUSIONS/SIGNIFICANCE: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01856205.