Pyogenic meningitis and viral encephalitis including JE are the most common causes of acute presentation with fever and encephalopathy. Preventive strategies must be directed keeping these causes in mind.

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BackgroundBacterial 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.MethodsIt 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.ResultsSerum 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.ConclusionSerum 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.

BackgroundOsteopetrosis is a rare inherited metabolic bone disorder characterized by extensive sclerosis of skeletons, visual and hearing impairment, hepatosplenomegaly and anemia. It has two major clinical forms: the autosomal dominant adult (benign) form is associated with milder symptoms often appearing in later childhood and adulthood whereas the autosomal recessive infantile (malignant) form has severe presentations appearing in very early childhood, if untreated, is typically fatal during infancy or early childhood. A rare autosomal recessive (intermediate) form is present during childhood with some signs and symptoms of malignant osteopetrosis. Diagnosis is mainly based on clinical and typical generalized increase in bone density.Case presentationThe two siblings of Indo-Aryan ethnicity, aged five and 8 years, were admitted with irregular low grade fever and gradually increasing abdominal mass for last 3 years. They also had history of hearing loss. On examination, the patients were found pale with poor nutritional status, short stature, frontal bossing and splenomegaly. We made a clinical diagnosis of hemolytic anemia and investigated accordingly. Peripheral Blood Smear was suggestive of leucoerythroblastic picture in both the siblings. We extended our investigations and radiological survey revealed generalized increase in bone density which was consistent with osteopetrosis.ConclusionOsteopetrosis is a rare disease transmitted by autosomal dominant or recessive inheritance having variable penetrance. We report here milder form of disease in the two siblings having typical clinical features in the form of anemia, hepatosplenomegaly and hearing loss. Diagnosis was confirmed by typical generalized increase in bone density in both the patients.

Background Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country. Methods We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to <2 years, 2 years to <18 years, and 18 years to 45 years), into one of four groups (A-D). Participants in groups A-C received a single dose (25 μg; 0•5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 μg; 0•5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A-C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and(2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97•5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A-C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of -10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99•17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0•67 and 1•50, which is the predefined equivalence margin recommended by WHO. The co-pri...

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.

Background:The understanding and management of neurological disorders is undergoing revolutionary changes over the last three decades in the background of ever increasing advances in medical technologies, diagnostic techniques, therapeutic processes and, molecular and genetic medicine. The fruits of these advances can reach patients only if the psychosocial hurdles in their delivery are identified, acknowledged and addressed.Aim:To explore the beliefs and practices of patients with neurological disorders in a tertiary care center in the eastern Nepal.Materials and Methods:One hundred patients attending neurology/medicine outpatient for neurological disorders were interviewed about their beliefs regarding the triggering factors, causation and treatment-seeking behavior particularly from traditional healers.Result:Of the 100 patients (49 males, 51 females) recruited in the study, 51% expressed having ‘no idea’ about their illness. Only 20% patients gave medically congruent explanation for their illness. Psychological factors were attributed as triggering factors by 16% of patients, of which two-thirds were females. Chance, destiny and ‘jadu tona’ topped the list of triggering factors. Forty-four percent patients had sought help of traditional faith healers (‘Dhami Jhakri’) before seeking medical help. Traditional faith healers were approached by patients irrespective of their educational background. Fifty-nine percent of patients who first sought traditional faith healers, believed in ‘jadu-tona’. Of those interviewed, 16% were planning to go to a faith healer in near future.Conclusion:The beliefs of patients with neurological disorders frequently do not conform to current medical opinion. There is need for greater communication and education of patients by their treating physicians.

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants' to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity. The initial site selection, set up and preparatory activities for the clinical trial are crucial to minimizing the risks to both participants and to successful completion during the subsequent study execution.In this paper, we describe the experience and lessons learned of building clinical trial site capacity in terms of infrastructure and human resource development for a Phase III vaccine clinical trial. We believe that sharing the experience of setting up a clinical trial in a resource-limited country will enable other entities contemplating clinical research in these countries, to prepare and plan ahead, to minimize the impact of barriers, and to contribute to bringing more studies to the countries where people live with the burden of vaccine-preventable, poverty-associated diseases.