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.

Typhoid Fever among Admitted Pediatric Patients in a Tertiary Care Center: A Descriptive Cross-sectional Study.

INTRODUCTION: Typhoid fever, an acute systemic febrile illness caused by Salmonella Typhi & Paratyphi, is an important public health problem in developing countries. It requires frequent observation regarding proper diagnostic protocol and treatment practices. The aim of the study is to find the prevalence of typhoid fever among admitted pediatric patients in a tertiary care center. METHODS: This is a descriptive cross-sectional study conducted among the admitted patients of pediatric and adolescent medicine of a tertiary care center from August 2016 to May 2018 after obtaining ethical clearance (IRC/609/015). Convenience sampling was used and data was analyzed using the Statistical Package of Social version 11.5. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Among 7450 patients, 151 (2.03%) at 95% Confidence Interval (1.71-2.35) patients were diagnosed with enteric fever of which 85 (56.29%) were male and 66 (43.71%) were female. Common symptoms were fever 151 (100%), and abdominal pain 94 (62.25%). Azithromycin 54 (38.03%) was the most common antibiotic received before presenting to hospital and ceftriaxone 151 (100%) was prescribed to all the patients after admission. Two-third of the patients (96/151) was hospitalized for at least 6 days, with the longest hospital stay of 14 days and shortest of 3 days. CONCLUSIONS: Occurrence rate of Typhoid Fever was similar to other studies. Antibiotic susceptibility could not be well established; further surveillance on typhoid fever and the antimicrobial susceptibility pattern is recommended.

Association of antithyroglobulin antibody with iodine nutrition and thyroid dysfunction in Nepalese children.

BACKGROUND: Aberrant iodine intake and thyroid autoimmunity affect thyroid function. Deficiencies of iodine including thyroid disorders have serious impact on child physical and mental development. This study was conducted to investigate iodine nutrition, thyroid function and thyroid autoimmunity in the Nepalese children, and explore the association of thyroidal autoimmunity with iodine nutrition and thyroid dysfunction. METHODS: Five schools from Udayapur district of eastern Nepal were selected for the study. A total of 213 school children aged 6-12 years were enrolled, and anthropometric data, urine samples and blood samples were collected. Urinary iodine concentration (UIC), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and antithyroglobulin antibody (TgAb) was measured. Independent T test, Man-Whitney test, Chi-square test and Fisher's Exact test were used for testing statistical significance. Spearman's correlation analysis was done to find association between variables. RESULTS: The median UIC with IQR, mean ± SD fT3, mean ± SD fT4, median TSH and TgAb with IQR was 150.0 µg/L (102.8; 204.0), 2.49 ± 0.83 pg/ml, 1.33 ± 0.42 ng/dl, 2.49 mIU/L (1.58; 4.29), and 21.40 IU/ml (15.54; 31.20) respectively. Elvated TgAb (≥30 IU/ml, thyroid autoimmune condition) was seen in 25.8% (n = 55) children. UIC was less than 100 µg/L in 17.4% (n = 37) of the children. Subclinical hypothyroidism, overt hypothyroidism and sublinical hyperthyroidism was seen in 1.4% (n = 3), 3.3% (n = 7) and 3.8% (n = 8) children respectively. A strong association of TgAb with UIC (r = - 0.210, p = 0.002) and thyroid hormones; fT3 (r = - 0.160, p = 0.019), fT4 (r = - 0.275, p < 0.001), and TSH (r = 0.296, p < 0.001) was seen. The relative risk for thyroid autoimmunity in children with UIC less than 100 µg/L was 1.784 (95% CI: 1.108-2.871, p = 0.024). Similarly, children with thyroid autoimmunity had higher relative risk [7.469 (95% CI: 2.790-19.995, p < 0.001)] for thyroid dysfunction. CONCLUSIONS: School children of eastern Nepal have adequate iodine nutrition. Thyroid autoimmunity is very common, while thyroid dysfunction is sparse in children. An association of thyroid autoimmunity with iodine nutrition and thyroid dysfunction was seen in children.

Pattern of renal diseases in children: A developing country experience.

Spectrum of renal disease varies in different ethnic population, geographical location, and by environmental factors. The purpose of this study was to find out the clinical spectrum and occurrence of different pediatric renal diseases at a teaching hospital in the Eastern part of Nepal. All cases of renal diseases from one month to 15 years of age, attending the pediatric renal outpatient department and/or were admitted to the wards during the period of February 2012 to January 2013, were included in the study. Detailed clinical and laboratory evaluations were performed on all patients. Diseases were categorized as per standard definitions and managed with hospital protocols. Renal diseases accounted to be 206 cases (6.9%) of total annual pediatric admissions, of which (58%) were male and (42%) female. Acute glomerulonephritis (AGN) was the most common disorder (37.7%) followed by nephrotic syndrome (26.1%), urinary tract infection (21.3%), acute kidney injury (AKI) (17.9%), obstructive uropathy (1.9%), chronic kidney disease (CKD) (1.2%), and others. In AGN group, the most common cause was post-infectious glomerulonephritis (PIGN) (32.9%) followed by lupus nephritis (4%) and Henoch-Schonlein purpura nephritis (0.8%). Urine culture was positive in (9.22%) and the most common organism was Escherichia coli (57.9%). The causes of AKI were urosepsis, septicemia, and AGN (18.9%) each, followed by dehydration (13.5%). Mortality was found in 5% of cases and the etiologies were AKI in (72.7%), PIGN (18.1%), and CKD (9%). Renal diseases are a significant problem among children and are one of the common causes of hospital admission. These patients need comprehensive services for early identification and management.

Osteopetrosis in two siblings: two case reports.

BACKGROUND: Osteopetrosis 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 PRESENTATION: The 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. CONCLUSION: Osteopetrosis 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.

Status of gastric lavage in neonates born with meconium stained amniotic fluid: a randomized controlled trial.

BACKGROUND: Neonates born with meconium stained amniotic fluid (MSAF) can develop feed intolerance during first few days of post -natal period. A randomized controlled trial was conducted with the objectives of to find out the incidence of feed intolerance in vigorous neonates with MSAF who received gastric lavage (GL) as compared to those in whom it was not performed. METHODS: This was a randomized controlled trial on 500 neonates satisfying the inclusion criteria, 230 were allocated to GL and 270 to no lavage group through computer generated random numbers. RESULTS: No significant difference in the incidence of vomiting was found between GL and no lavage group (8.7 % vs 11.5 %, p = 0.305). Feed intolerance had no relationship with gestational age, gender, birth weight and mode of delivery. No neonates of GL group developed any complications related to the procedure. CONCLUSION: Thus, it may be concluded that gastric lavage is not required in neonates born with MSAF.

Subclinical Hypothyroidism and Elevated Thyroglobulin in Infants with Chronic Excess Iodine Intake.

BACKGROUND: Acute iodine excess in newborns can cause hypothyroidism, but there are limited data on the effects of iodine excess on thyroid function in older infants. The aim of this study was to measure the effects of chronic excess iodine intake on thyroid function in 6-24-month-old infants. METHODS: In this cross-sectional study, infants (n=696) in eastern Nepal were studied. Spot urine samples, venous blood samples, and household salt samples were collected, and urinary iodine concentration (UIC), serum free thyroxine (fT4), thyrotropin (TSH), thyroglobulin (Tg), and titrated household salt iodine concentration (SIC) were measured. Daily iodine intake was calculated from UIC based on estimates of urine volume at this age. RESULTS: Median (25th-75th percentile) household SIC was 89 (70-149) ppm, while national legislation stipulates a fortification level of 50 ppm. Median UIC was 407 (312-491) µg/L; 76% of infants had a UIC >300 µg/L, suggesting iodine excess. Calculated mean iodine intake in 12-24-month-old infants was 220 µg/day, exceeding the recommended safe upper limit for iodine at this age (200 µg/day). Among the infants, 15.8% had an elevated Tg, 7.4% had subclinical hypothyroidism, but <1% had overt hypothyroidism. UIC was not a significant predictor of thyroid function, thyroid hormones, or Tg. CONCLUSION: In 6-24-month-old infants exposed to excessive iodine intake, ∼7% have subclinical hypothyroidism but <1% have overt hypothyroidism. These findings suggest the thyroid in late infancy is already able to adapt to high iodine intakes and, in most cases, maintain euthyroidism.

Atypical clinical presentation of mucopolysaccharidosis type II (Hunter syndrome): a case report.

INTRODUCTION: We present a very rare case of mucopolysaccharidosis with atypical presentation such as mild mental retardation, an acrocephalic head and no corneal clouding. The purpose of presenting this case is to highlight the distinctive manifestation of mucopolysaccharidosis type II (Hunter syndrome). CASE PRESENTATION: A 10-year-old East Asian boy presented with abdominal distension of five years' duration and complained of shortness of breath on and off for the same period. On examination his head was large and his head circumference was 54.5 cm. His neck was short, he had coarse facial features, a depressed nasal bridge and small stubby fingers with flexion of distal interphalangeal joints, and a low arched palate was observed. There was mild mental retardation. CONCLUSION: Based on clinical findings and radiological features it is possible to diagnose a case of mucopolysaccharidosis.Careful and systemic approach is needed to accurately diagnose the exact type as enzymatic studies are not available in most centers.