Clinical Profile and Outcome of Chronic Pancreatitis in Children.

Objective: To evaluate the etiology, presentation, complications and management of chronic pancreatitis in children. Design: Retrospective chart review. Setting: Gastroenterology department at Christian Medical College and Hospital, Vellore, India between January 2005 and December 2010. Participants: 99 Children (<18 yrs) diagnosed with chronic pancreatitis based on clinical and imaging features. Main outcome measures: Etiology, clinical presentation, complications and management of chronic pancreatitis in children. Results: Of 3887 children who attended the Gastroenterology department, 99(2.5%) had chronic pancreatitis, of which 60 (60.6%) were males. In 95(95.9%) patients no definite cause was detected and they were labeled as Idiopathic chronic pancreatitis. All patients had abdominal pain, while 9(9.1%) had diabetes mellitus. Of the 22 children tested for stool fat, 10(45.5%) had steatorrhea. Pancreatic calcification was seen in 69 (69.7%). 68 (71.6%) patients with idiopathic chronic pancreatitis had calcification. Calcific idiopathic chronic pancreatitis was more frequent in males (67.6% vs. 48.1%, P=0.07), and was more commonly associated with diabetes mellitus (13.2% vs. none, P=0.047) and steatorrhea (61.5% vs. 16.7%, P=0.069). Pseudocyst (17.1%) and ascites (9.1%) were the most common complications. All children were treated with pancreatic enzyme supplements for pain relief. 57 patients were followed up. With enzyme supplementation, pain relief was present in 32 (56.1%) patients. Of those who did not improve, 10 underwent endotherapy and 15 underwent surgery. Follow up of 8 patients who underwent endotherapy, showed that 5 (62.5%) had relief. Follow up of 11 patients who underwent surgery showed that only 3 (27 %) had pain relief. There was no death.

Immunogenicity and Safety of a DTaP-IPV//PRP~T Vaccine (Pentaxim) Booster Dose During the Second Year of Life in Indian Children Primed with the Same Vaccine.

Objective: To evaluate the immunogenicity and safety of a pentavalent (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate) combination vaccine booster dose. Design: Multicenter, open, Phase III clinical study. Setting: Two tertiary-care hospitals in Delhi and Vellore, India. Participants/patients: 207 healthy Indian children. Intervention: The DTaP-IPV//PR~NT vaccine (Pentaxim) was given at 18-19 months of age to children who had been primed with the same vaccine at 6,10,14 weeks of age. Main outcome measures: Immunogenicity was assessed before and 1 month after the booster. Safety was evaluated from parental reports, and investigator assessments. Results: At 18-19 months of age, before boosting, the SP rates against diphtheria, tetanus, poliovirus and PRP were 82.3-100%; 90.0% of participants had anti-PRP ≥0.15 μg/mL. Anti-poliovirus titers were ≥1:8 dilution in 97.9-98.4% of participants. Anti-PT and FHA titers (≥5 EU/mL) were detectable in 82.5% and 90.8% of participants, respectively. One month after the booster dose, SP rates were 99.5% for PRP (≥1.0 μg/mL), 100% for diphtheria, tetanus (≥0.1 IU/mL) and polioviruses (≥8:1/dilution). Seroconversion (4 fold post-booster increase in anti-PT and -FHA concentration) occurred in 96.8% and 91.7%, respectively. Geometric mean concentrations (GMC) increased from 11.7 to 353.1 EU/mL and from 18.2 to 363.4 EU/mL for anti-PT and anti- FHA, respectively. Anti-PRP GMC increased from 1.75 to 70.5 μg/ mL. Vaccine reactogenicity was low; severe solicited reactions were reported by <1.4% of participants. Conclusion: The DTaP-IPV//PRP-T vaccine booster at 18-19 months of age was well tolerated and induced strong antibody responses.

Validation of IMNCI Algorithm for Young Infants (0-2 months) in India.

Objective: To check the validity of Integrated Management of Neonatal and Childhood Illness (IMNCI) algorithm for young infants (0-2 months). Design: Prospective observational study. Setting: The outpatient department and emergency room of a medical college attached hospital. Methods: 419 infants (176 between 0-7 days, 243 between 7 days–2 months) underwent a detailed diagnostic assessment and treatment as per the standard protocol of treating unit. These infants also underwent assessment, classification and identification of treatment as per IMNCI algorithm. The diagnostic and therapeutic agreement between standard protocol and IMNCI was computed to assess the validity of IMNCI algorithm. Results: The IMNCI algorithm performed well in identifying sick young infants with sensitivity of 97%, 94% and 95%, and specificity of 85%, 87% and 87% in 0-7 days, 7 days–2 months and 0-2 months age groups, respectively. The algorithm covered majority (80%) of recorded diagnoses, and could identify bacterial infection with 88.5% sensitivity and 57.4% specificity. Complete diagnostic agreement with gold standard was seen in 50%; overdiagnosis and under diagnosis was seen in 13% and 19%, respectively. Low birthweight and upper respiratory infection were the main reasons for overdiagnosis whereas surgical conditions resulted in under diagnoses in majority. Conclusion: IMNCI algorithm for evaluation and management of young infants has good sensitivity and specificity for referring cases with severe illness.

Dyslipidemia and Superoxide Dismutase Activity in Children with Down Syndrome.

Introduction: Down Syndrome (trisomy 21) provides an interesting natural model to study atherosclerosis, since these individuals appear to be protected from plaque formation. Methodology: We assessed the lipid levels, and superoxide dismutase (SOD) activity in 32 clinically diagnosed children of Down syndrome and 34 children matched for age and sex as controls. Results: SOD activity was found to be significantly higher (p=0.004) in children with Down Syndrome (mean=313.7 IU/ml) than in controls (mean140.2 IU/ ml). Significantly higher levels of serum triglyceride (154.7 mg/dl) and VLDL (33.9 mg/dl) were observed in Down Syndrome as compared to healthy controls (119.6 mg/dl and 23.9 mg/dl respectively; p<0.05 for each). However, the two groups did not show any significant difference in levels of serum HDL-C, LDL-C. Conclusion: The raised antioxidant activity of SOD, because of over expression of genes situated non chromosome 21, probably offers some protection against the development of atherosclerosis despite the occurrence of dyslipidemia.

Assessment of dietary compliance to gluten free diet and psychosocial problems in indian children with celiac disease.

Objective. To assess dietary compliance to Gluten Free Diet (GFD), to identify barriers to compliance and to study the impact of diet on the psychosocial behavior of children with celiac disease. Methods. Children diagnosed with celiac disease and followed up for more than 6 months, were assessed for dietary compliance. After this assessment, patients were subjected to an interview, consisting of self administered questionnaire, by the investigator who was blinded to initial results of initial assessment. Psychosocial parameters were assessed by standard Pediatric Symptom Checklist (PSC) containing 35 items. Dietary compliant and non-compliant groups were compared for assessed factors affecting the dietary compliance. Cases were also compared to healthy controls for psychosocial parameters. Results. A total of 70 patients were assessed for dietary compliance: 53(75%) were found to be dietary compliant, 13(18%) dietary non-compliant while 4 had doubtful dietary compliance. Final analysis was done for 64 patients who had complete assessment; 4 patients with doubtful dietary compliance and 2 patients who had incomplete assessment, were excluded. Dietary compliance was higher in younger children (>80%) compared to adolescents (44%); in children with higher maternal education; in parents having better knowledge and understanding of disease. Compliance was better in nuclear families; with less number of siblings (68.3% of compliant had <2 siblings compared to 23% in non- compliant); in families with higher per capita income. Dietary compliance was also better in children who presented with typical symptoms of celiac disease (72% of dietary compliant presented with loose motion as presenting symptom compared to only 15% in non-compliant). Celiac children had problems related to adjustment such as difficulty in maintaining diet at school, restaurants, trips, etc.45% patients complained that their teachers don’t understand the nature of their disease. Pediatric Symptom Checklist (PSC) score was above cut-off in 4 children of dietary non-compliant group. Few individual PSC items such as complaints of aches and pains; is irritable, angry; does not listen to the rules, blames other for mistakes; teases others; refuses to share, were more common in celiac children than control. Conclusions. Noncompliance to gluten free dietary regimen is seen in18 % of cases. Dietary noncompliance is more common in the adolescent age group, in joint families and those who have more number of siblings. Dietary restrictions have impact on child’s social activities and thus psychosocial parameters (PSC score) are better in the dietary compliant group.

Cytokine gene polymorphisms in Irritable bowel syndrome in Indian population - A pilot case control study.

Aim: This study aimed at evaluating the single nucleotide polymorphisms (SNPs) in five cytokine genes regulating inflammation at altogether 8 different loci and compared their frequencies in patients with Irritable bowel syndrome (IBS) versus healthy age and sex matched controls. Methods: Peripheral blood was collected for DNA cytokine analysis from 23 patients with IBS and 20 healthy controls. The cytokine SNPs studied include TNF-á (-308G/A), TGF-â1 (codon10T/C, codon25G/C), IL-10 promoter (-1082A/G; -819T/C; -592A/C), IL-6 promoter (-174G/C), and IFN-ã (+874T/A). Results: There was a significant difference between a SNP in IL-10 (-592A/C) among cases and controls. There was also a trend to significance as regards to IL-6 promoter (-174G/C). Frequencies of other SNPs were not significantly different between the two groups. Conclusion: This pilot study shows that there are polymorphism differences in cytokine genes between patients with IBS and healthy controls from India.

Immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type b conjugate combination vaccine (pentaxim™) with hepatitis B vaccine.

Objective: To obtain immunogenicity and safety data for a pentavalent combination vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate). Design: Multicenter, open, Phase III clinical study. A DTaP-IPV//PRP~T vaccine (PentaximTM) was given at 6,10,14 weeks of age; and Hepatitis B vaccine at 0,6,14 or at 6,10,14 weeks of age. Immunogenicity assessed 1 month post-3rd dose; safety assessed for 30 minutes by the investigator, then by parents and investigators to 8 days and 30 days post-vaccination. Setting: Tertiary-care hospitals. Participants/patients: 226 healthy Indian infants (6 weeks of age). Main outcome measures: Immunogenicity and safety. Results: Immunogenicity was high for each vaccine antigen, and similar to a historical control study (France) following a 2,3,4 month of age administration schedule. Post-3rd dose, 98.6% of subjects had anti-PRP ³0.15 mg/mL and 90.0% had titers ³1.0 mg/mL; the anti-PRP GMT was 4.1 µg/mL. Seroprotection rates for diphtheria and tetanus (³0.01 IU/mL) were 99.1% and 100%; and 100%,99.1% and 100%, for polio types 1,2 and 3 (³8 [1/dil]) respectively. Anti-polio GMTs were 440.5,458.9, and 1510.7 (1/dil) for types 1,2 and 3 respectively. The vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 93.7% for PT and 85.7% for FHA; the 2-fold increase was 97.1% and 92.4%. Vaccine reactogenicity was low with adverse reaction incidence not increasing with subsequent doses. Conclusion: The DTaP-IPV//PRP~T vaccine, given concomitantly with monovalent hepatitis B vaccine, was highly immunogenic at 6, 10 and 14 weeks of age in infants in India. The vaccine was well tolerated.

Pediatric inflammatory bowel disease in south India.

Among 34 children diagnosed to have inflammatory bowel disease (IBD) over past 8 years, 23 had Crohn’s disease and 11 had ulcerative colitis. Pediatric patients accounted for 7% of new cases of IBD seen annually. Median delay in diagnosis was 15 months. Nutritional impairment was significantly more common in Crohn’s disease.

Antithymocyte globulin and cyclosporin in children with acquired aplastic anemia.

OBJECTIVE: To assess the responses to ATG and cyclosporin combination in patients of aplastic anemia. METHODS: Twenty three (17M: 6F) patients of aplastic anemia (11 very severe aplastic anemia (VSAA) and 12 severe aplastic anemia (SAA), were administered antithymocyte globulin and cyclosporin. RESULTS: The median age of patents was 8 years (range 6-12 years). Three patients died within 2 months of therapy. Twenty children (11 SAA and 9 VSAA) were finally analysed. Six months after the start of treatment, 8/20 (40%) patients responded-2 complete (CR) and 6 partial responses (PR). At the end of 1 year; 2 patients maintained CR and seven patients continued PR (overall responders 45%). The response was better in SAA (54.5%) with 2 CR and 4 PR; than in VSAA (33%) with 3 PR . Eleven (55%) children were alive without response. One patient developed AML 13 months later. CONCLUSION: We conclude that antithymocyte globulin and cyclosporin combination is an effective treatment for aplastic anemia patients who are ineligible for bone marrow transplantation.

Meningococcal disease--outbreak in Delhi.

Meningococcal disease occurs both endemically and epidemically across the world. In India also meningococcal disease occurs sporadically with epidemics occurring at regular intervals. Epidemics of meningococcal disease have occurred in Delhi in the year 1935, then in the year 1966 which lasted for a year and again in 1985-86. The last epidemic took a great toll with case fatality rate nearly 13%. This year also there has been an outbreak of meningococcal disease with nearly 400 cases and case fatality rates of about 10% majority are males between the age group of 21-30 years and from the inner crowded areas of the city.

Congenital diaphragmatic hernia: delayed presentation with asymptomatic spleenic herniation.

Patients with congenital diaphragmatic hernia (CDH) usually present in the immediate neonatal period with respiratory distress. Presentation beyond the neonatal period has, however, been reported. We report a case of a 3-year-old child who presented with a six months history of respiratory symptoms and had been subjected to a variety of therapies like antibiotics, antitubercular medication and two attempts at putting an intercostal tube, as radiographs were suggestive of pleural effusion. This study highlights the importance of a high index of suspicion, relevance of thorough clinical examination and non-invasive diagnostic modalities along with an uncommon occurrence of asymptomatic spleenic herniation at such a later age. Spleenic herniation is rare outside neonatal period.

Typhoid vaccines.

Typhoid fever continues to be a major public health problem in developing countries with about 33 million cases per year. Protective efficacy of traditional acetone/phenol killed vaccines is similar to newer typhoid vaccines (Ty21A and Vi antigen vaccine) but side effects of these newer vaccines are considerably less. Though the mortality is low, typhoid fever causes considerable morbidity and loss of working days. Problems during treatment are increasing due to emergence and spread of multidrug resistant S. typhi. Hence to decrease the incidence of typhoid fever in addition to ensuring safe water supply and excreta disposal a typhoid vaccine needs to be introduced in the National Immunization Schedule.

Rational antibiotics therapy in bacterial meningitis.

Acute bacterial meningitis is one of the most important causes of morbidity and mortality in developing countries. Though a wide range of antibiotics is available for therapy, judicious and rational use of antimicrobial agents needs to be ascertained. The choice of antimicrobial agents depends mainly on the age of the patient and its CSF penetrability. Neonatal meningitis is commonly caused by Gram Negative organisms such E. coli, Klebsiella and Pseudomans;Group B streptococciand Listeria, though other organisms like Staphylococcus sp. also contribute. The neonatal meningitis is best treated with a combination of amplicillin and a third generation cephalosporin given for 14-21 days. Post-neonatal meningitis usually occurs due to S. pneumoniae, N. meningitidis and H. influenzae and is best treated with third generation cephalosporins used with or without crystalline penicillin or ampicillin depending on the clinical situation. The therapy should be modified, if necessary, on availability of culture sensitivity report. The use of dexamethasone in meningitis due to the organisms other than H. influenzae still remains controversial.

Pulmonary function tests in beta thalassemia.

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes--functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates--forced expiratory volume in one second (FEV1), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.