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.

Dental Caries on Deciduous Molars among Children Visiting Dental Outpatient Department of a Tertiary Care Centre.

Introduction: Dental caries is one of the most common, yet preventable childhood diseases. The aetiology of dental caries lies in the interplay between host, microorganism, substrate, and time. Risk factors for dental caries include physical, biological, environmental, behavioural, and lifestyle-related factors such as high numbers of cariogenic bacteria, inadequate salivary flow, insufficient fluoride exposure, poor oral hygiene, inappropriate methods of feeding infants, and poverty. The aim of the study was to find out the prevalence of dental caries on deciduous molars among children visiting dental Outpatient Department of a tertiary care centre. Methods: This descriptive cross-sectional study was conducted on children who visited the dental outpatient department of Kathmandu University School of Medical Sciences, Dhulikhel Hospital from 15 June 2023 to 30 July 2023. Ethical approval was taken from the Institutional Review Committee of the same institute. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: The prevalence of dental caries on deciduous molars in children was 252 (93.33%)(90.35-96.30, 95% Confidence Interval). One-third of the children had visited dental clinics for the first time. Lack of topical fluoride application was seen in the majority of the children. Conclusions: The prevalence of dental caries on deciduous molars among pediatric patients was found to be higher than in other studies done in similar settings. Keywords: children; dental caries; molars; prevalence.

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.

Congenital Hypothyroidism among Infants Undergoing Thyroid Function Test in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Congenital hypothyroidism is the most preventable and treatable cause of mental retardation in newborns and infants. Screening for congenital hypothyroidism in newborns and infants is not a routine practice in our part of the world. This study aimed to find out the prevalence of congenital hypothyroidism among infants undergoing thyroid function test in a tertiary care centre. Methods: A descriptive cross-sectional study was done in the Department of Biochemistry, from laboratory records starting 14th April, 2013 to 13th April, 2020 after obtaining ethical clearance from the Institutional Review Committee (Reference number: 1502/019). Data of infants whose thyroid function tests were performed were obtained using convenience sampling. Thyroid-stimulating hormone was categorised per the European Society of Paediatric Endocrinology guidelines. Data were entered and analysed using Microsoft Excel 2011 and the Statistical Package for the Social Sciences version 11.5. Point estimate at a 95% Confidence Interval was calculated along with frequency and percentages for binary data. Results: Among 1243 infants, 56 (4.50%) (3.35-5.65 at 95% Confidence Interval) infants were diagnosed with congenital hypothyroidism. Conclusions: The prevalence of congenital hypothyroidism was higher than other studies done in similar settings. An unexpected finding of treatment-induced hyperthyroidism was observed, indicating a lack of regular and timely follow-up of infants diagnosed with congenital hypothyroidism. Keywords: congenital hypothyroidism; Nepal; newborn screening; prevalence.

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.

Tobacco and its Relationship with Oral Health.

Tobacco and its various forms cause major oral health problems. Tobacco either in smoked or smokeless forms is prevalent in Nepal and counts as a risk factor for the causation of various red and white lesions, premalignant lesions, oral cancers, gingival and periodontal diseases. Tobacco in conjunction with other risk factors adds a potential threat to oral diseases and its timely control is a cure to those threats. This article focuses on tobacco and its forms affecting oral health and also focuses on its prevention and control from the ground to the National level.

Psychological Effects of COVID-19 and Its Measures in Nepalese Medical Students.

Having to listen to the devastating daily news brought by COVID-19 since the first case was reported on 23rd January 2020 in Nepal, it has pushed the country into various crises. The issue of psychological health has been overlooked during this crisis.COVID-19 has sabotaged the psychological health of general people and more importantly medical students. It has disrupted the academics and clinical rotations of medical education. The prospect of being the future health care personnel without adequate training has destroyed the confidence and aspiration andin addition, joining the frontline against this type of deadly virus with little preparedness has instilled fear and uncertainty among them. So, concerning the context, this article focuses on the psychological effects faced by medical students and some ways to overcome this issue. Keywords: psychological effects;medical students;COVID-19.

Neonatal mortality risk assessment using SNAPPE- II score in a neonatal intensive care unit.

BACKGROUND: There are many scoring systems to predict neonatal mortality and morbidity in neonatal intensive care units (NICU). One of the scoring systems is SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal extension-II). This study was carried out to assess the validity of SNAPPE-II score (Score for Neonatal Acute Physiology with Perinatal Extension-II) as a predictor of neonatal mortality and duration of stay in a neonatal intensive care unit (NICU). METHODS: This prospective, observational study was carried out over a period of 12 months from June 2015 to May 2016. Two hundred fifty five neonates, who met the inclusion criteria admitted to NICU in tertiary care hospital, BPKIHS Hospital, Nepal were enrolled in the study and SNAPPE-II score was calculated. Receiver Operating Characteristic (ROC) curve was constructed to derive the best SNAPPE-II cut-off score for mortality. RESULTS: A total of 305 neonates were admitted to NICU over a period of one year. Among them, 255 neonates fulfilled the inclusion criteria. Out of 255 neonates, 45 neonates (17.6%) died and 210 were discharged. SNAPPE-II score was significantly higher among neonates who died compared to those who survived [median (IQR) 57 (42-64) vs. 22 (14-32), P < 0.001]. SNAPPE II score had discrimination to predict mortality with area under ROC Curve (AUC): 0.917 (95% CI, 0.854-0.980). The best cut - off score for predicting mortality was 38 with sensitivity 84.4%, specificity 91%, positive predictive value 66.7% and negative predictive value 96.5%. SNAPPE II score could not predict the duration of NICU stay (P = 0.477). CONCLUSION: SNAPPE- II is a useful tool to predict neonatal mortality in NICU. The score of 38 may be associated with higher mortality.

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.

Head growth of undernourished children in rural Nepal: association with demographics, health and diet.

BACKGROUND: Brain development in early childhood is a key determinant of later cognition, social achievement and educational success. Head circumference (HC) measurements are a simple method to assess brain growth, yet reports of these measurements are uncommon in nutritional surveys of undernourished children. OBJECTIVE: To evaluate HC measurements in a population of rural Nepali children and relate these measurements to demographics, health and diet. METHODS: An observational study of head growth was nested within a longitudinal evaluation of a livestock-based agricultural intervention in rural Nepal. Between 538 and 689 children (aged 6 months to 8 years) were measured (height, weight, HC) at each of six survey visits. A total of 3652 HC measurements were obtained. Results were converted to Z-scores (WHO Anthro). RESULTS: Mean head circumference Z-scores (HCZ) diminished progressively over the first 4 years of life; a decline of 30% occurred between 3 and 4 years of age (-1.73 to -2.45, P < 0.0001). Overall, 56% of HCZ were <-2. Gender-adjusted HCZ (but not other measurements) were significantly lower for girls than boys [mean (SD) -2.31 (1.0) vs -1.99 (0.094), P < 0.0001]; girls more often had microcephaly (61% vs 50%, P < 0.0001). For children <3 years of age, HCZ were better in those who had eaten two or more animal-source foods (ASFs) within the previous 24 h [-1.69 (.05) vs -2.08 (0.10), P = 0.001] than in those who had eaten none or only one; HCZ correlated with the number of ASFs consumed (P < 0.001). Regression analyses demonstrated that the main determinants of HCZ were age, weight-for-age Z-scores (WAZ) and gender; 43% of the variance in HCZ in younger children was explained by WAZ and ASF consumption. CONCLUSION: HCs reflect brain size in young children; brain size is linked to cognitive function. Poor head growth represents another facet of the 'silent emergency' of child undernutrition. Routine HCZ assessments may contribute to better understanding of the links between poverty and cognitive development.

Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 .

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.

Assessment of control of bronchial asthma in children using Childhood Asthma Control Test.

BACKGROUND: The use of Childhood Asthma Control Test (C-ACT) has been advised for monitoring asthma control by the Global Initiative for Asthma (GINA) guidelines. OBJECTIVE: To validate the tool C-ACT for the assessment of control of asthma and to examine the correlation between C-ACT score and lung function assessed by forced expiratory volume in one second (FEV1). METHODS: This was a prospective observational study conducted between January 2010 to January 2011. Children diagnosed to have bronchial asthma and aged 5 to 14 years, were enrolled in the study. Asthma severity and control status were classified according to the National Asthma Education and Prevention Programme (NAEPP) and GINA guidelines, respectively. Patients were followed-up at three and six months and C-ACT and spirometric measurements were obtained. RESULTS: Significant positive correlations were found between C-ACT score and FEV1 at enrollment (r = 0.772) (p < 0.001), three months (r = 0.815) (p < 0.001) and at six months follow-up (r = 0.908) (p < 0.001). Baseline C-ACT score was useful for predicting the levels of control of asthma upto three months (0.004), but not at six months follow-up (0.787). A cut-off C-ACT value of > or = 19 had a sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) 98.5%, 89.1%, 94.9%, 96.6%, 0.717, respectively for the control of asthma. CONCLUSION: C-ACT is a simple and feasible tool to assess and predict the levels of control in children with bronchial asthma upto three months.

Clinical and ultrasonographic measurement of liver size in normal children.

OBJECTIVES: To measure the normal range of dimensions of liver in children of various age groups and to compare the liver measurement obtained by palpation-percussion, auscultation and ultrasonography. METHODS: This was a cross-sectional comparative study in which 500 normal (weight for height between ± 2 SD of WHO standards for children aged less than 5 y and BMI between ± 2 SD of WHO standards for children aged more than 5 y) children (0-15 y) divided in 5 age groups (100 in each age group). Subjects were enroled from normal hospital delivery neonates, children visiting immunization and well baby clinics, children visiting outpatient and inpatient department with minor illnesses and healthy school children. RESULTS: The normal range of dimensions of liver in children were estimated and percentile tables of liver size were established. Though the measurements obtained by clinical methods were significantly (P < 0.001) lower than those obtained by ultrasonography, there was a strong correlation between clinical and ultrasonographic measurement. Palpation-percussion method could estimate the liver size within ± 1.0 cm of what was obtained by ultrasonography in 88 % of cases. In more than half of the study children (54.2 %), this estimation was within ± 0.5 cm. CONCLUSIONS: Clinical methods of liver span estimation strongly correlate with ultrasonographic measurement. The performance of palpation-percussion method is better than that of auscultation. Clinical methods should continue to be used for the estimation of liver size.

Urinary screening for detection of renal abnormalities in asymptomatic school children.

BACKGROUND: Urinary screening tests for early detection of renal diseases in asymptomatic school children and adolescents are important in the detection of silent renal diseases. OBJECTIVES: The purpose of the study was to determine the prevalence of occult renal diseases by dipstick test (reagent strips) in asymptomatic Nepalese children. PATIENTS AND METHODS: A total of 2,243 school children, aged 5-15 years, were screened for urinary abnormalities using dipstick test screening. The children who tested positive in the first screening were re-tested after 2-4 weeks. RESULTS: In the first screening, 123 children (5.5%) tested positive for isolated hematuria and proteinuria and for combined hematuria and proteinuria. Of these children, 16 (0.71%) cases tested positive in a second screening. Subsequently, 1 child from the secondary screening group was lost to follow up, 5 tested normal and 10 revealed abnormalities. Glomerulonephritis was the most commonly detected disorder (50%). CONCLUSIONS: Urinary screening was found to be useful in identifying occult renal diseases in asymptomatic children. Urinary screening would therefore not only help in early detection but also in the prevention of the deterioration of renal function later in life.