Acute Hyponatremia And Hypernatremia Related To Intravenous Fluid Administration In Hospitalized Children: A Randomized Observational Study

Background: Intravenous fluid and electrolyte therapy in most of the acutely ill hospitalized children has beenthe cornerstone of medical practice for a well over 50 years.Objective: To determine optimal maintenance fluid therapy by comparing the incidence of hyponatremia orhypernatremia in hospitalised children.Methods: A prospective Randomized study done in PICU in patients admitted to paediatric emergency. The studywas conducted between September 2007 to May 2008. Children of age group 1 month to 16 years were included.The fluid groups were divided into four groups. SPSS version 18 was used for analysis.Results: The mean age in group I is 4.42, in group 2 is 3.84, in group 3 is 3.67 and in group 4 is 4.45. The meanserum sodium levels in fluid group 1 is 137.4 mmol/L, in fluid group II 138.2 mmol/L, in fluid group III is 138.9mmol/L and fluid group IV is 137.8 mmol/L. After initiating maintenance fluid therapy serum sodium levelschanged in each group. As we can see in group 1 mean serum sodium level at the start of the therapy is 137.43mmol/L and after 24 hours of hypotonic fluid infusion it reduced to 135.4 mmol. 69 patients had hyponatremiaand 44 had hypernatremia.Conclusion: Amount of free fluid in the IV maintenance fluid can be factor in causing hypernatremia. Caution iswarranted to guard off a rapid fall of serum sodium level.

Recurrent benign copy number variants & issues in interpretation of variants of unknown significance identified by cytogenetic microarray in Indian patients with intellectual disability.

Background & objectives: Cytogenetic microarray (CMA) is now recommended as a first-tier clinical diagnostic test in cases with idiopathic intellectual disability and/or developmental delay (ID/DD). Along with clinically relevant variants, CMA platforms also identify variants of unknown significance (VUS). This study was done to look for utility and various issues in interpretation of copy number variants (CNVs) in Indian patients with ID/DD. Methods: The CMA was performed in 86 Indian patients with idiopathic ID/DD with or without dysmorphic features. CNV was reported if copy number gain was >400 kb in size and copy number loss was > 200 kb in size. Results: Pathogenic CNVs were found in 18 of 86 (20.9%) patients. One large (14 Mb size) de novo heterozygous copy number gain was found in one patient. VUS (total 31) were present in 17 of 86 (19.7%) patients. Five novel recurrent benign CNVs were also present in our patients. Interpretation & conclusions: Our findings highlight the difficulties in interpretation of CNVs identified by CMA. More Indian data on VUS and recurrent benign CNVs will be helpful in the interpretation of CMA in patients with ID/DD.

Influenza virus genotypes circulating in and around Lucknow, Uttar Pradesh, India, during post pandemic period, August 2010 - September 2012.

Background & objectives: During the post influenza pandemic period, continuous surveillance of influenza virus and its subtypes is mandatory to help the policy makers to take effective and appropriate decisions. Therefore, this study was planned to determine the pattern of influenza virus activity in context to various meteorological and clinical parameters in and around Lucknow, Uttar Pradesh, India, during post pandemic period August 2010 - September 2012. Methods: Nasal swabs/throat swabs/nasopharyngeal aspirates of 2669 patients were collected. One-step real time PCR for detection of influenza virus was done according to the Centers for Disease Control and Prevention (CDC) protocol. Results: Influenza positivity was 15.8 per cent (423/2669) in symptomatic patients. Of the 423 total positives, 192 (7.2%) were influenza A and 231 (8.7%) were influenza B. Positivity for influenza virus was significantly (P=0.001, OR=2.9, CI=1.9-4.3) higher in patients with Influenza like illness (ILI) (17.4%, 396/2271) than those with severe acute respiratory illness (SARI) (6.8%, 27/398). Influenza A positive samples were subtyped as; pdmH1N1 (67.2%, 129/192) and seasonal H3N2 (32.8%, 63/192). It significantly correlated with monthly mean rainfall, humidity and dew point while atmospheric pressure was inversely related. No significant association was found with temperature and wind speed. Clinical variations were observed between different strains of Influenza virus. Interpretation & conclusions: The findings provide a clear picture of different clinical presentations of various strains of influenza A and B viruses and epidemiology of influenza infection from Lucknow (UP), India. The seasonality of influenza virus infection showed variation in relation to different environmental factors. Pandemic H1N1 caused more systemic infection than seasonal influenza A/H3N2 virus.

Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients.

Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fl uorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.

Prospective multi-centre sentinel surveillance for Haemophilus influenzae type b & other bacterial meningitis in Indian children.

Background & objectives: Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance. Methods: Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per μl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens. Results: A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively). Interpretation & conclusions: Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.

Consensus Guidelines on Evaluation and Management of Suspected Acute Viral Encephalitis in Children in India.

Justification: Viral encephalitis is an important cause of mortality and morbidity in children. The etiological agents are varied, and physicians treating such children often feel limited by the lack of uniform guidelines on evaluation and management of these critically ill children in resource-constrained settings. Process: An ‘Expert Group Meeting on Viral Encephalitis in Children’ was held on 19th January, 2012 in Gurgaon, Haryana (under the aegis of PEDICON 2012, the National Conference of Indian Academy of Pediatrics). The invited experts included pediatricians and microbiologists with expertise in the relevant field. Various issues related to the subject were discussed and it was decided to bring out recommendations on the topic. The final recommendations were produced after circulating the draft document, and incorporating/discussing all changes, by e-mail. Objectives: To aid the pediatrician in the evaluation and management of children with suspected viral encephalitis and to assist the public health authorities in acute encephalitis surveillance. These guidelines do not cover viral encephalitis in the neonatal period and in immunocompromised children, Rabies encephalitis, and chronic viral encephalitis such as Subacute sclerosing panencephalitis (SSPE). Recommendations: Recommendation for evaluation and management of suspected viral encephalitis in children are presented. In any acute encephalitis outbreak, pediatricians should be aware of the common viral causes of encephalitis in their area, what information and samples they should collect, and the contact details of the District Surveillance Unit. Pending specific diagnosis and therapy (which may or may not be possible), prompt empirical therapy and meticulous supportive care are important to prevent ongoing brain damage, and improve outcome.

Aetiologic spectrum of mental retardation & developmental delay in India.

Background & objectives: The aetiology of mental retardation is varied and difficult to establish. Reports from India on the spectrum of underlying causative conditions are lacking. This retrospective study was conducted to establish the various aetiologies of mental retardation (MR) and developmental delay (DD) in patients attending a medical genetics centre in north India and to assess the contribution of genetic disorders. Methods: This retrospective study was conducted at a tertiary care centre in north India. All patients attending the centre with MR or DD from January 2007 to December 2009 were included. The aetiology of MR/DD was ascertained after clinical assessment and targeted laboratory evaluation. The spectrum of causative conditions and contribution of genetic disorders was established. Results: A total of 338 patients were included in the study, of whom definite diagnosis was established in 253 (74.8%). The various aetiological categories were: chromosomal disorders in 112 (33.1%), non chromosomal syndromes in 32 (9.5%), neurometabolic disorders in 34 (10.1%), central nervous system structural defects in 25 (7.4%), cerebral palsy in 43 (12.7%) and environmental insults in 7 (2%). Eighty five patients (25.2%) had idiopathic mental retardation. A total of 196 (58%) patients had a genetic disorder as the cause of MR/DD. Interpretation & conclusions: The aetiology of MR/DD is varied and difficult to establish in a significant proportion of patients. Chromosomal and various monogenic disorders contribute to a large number of MR/DD cases and hence a genetic work up is essential for all such patients.

Antibiotic resistance pattern of group-a beta-hemolytic streptococci isolated from north Indian children.

Background: The current resistance pattern of GABHS (group-A beta-hemolytic streptococci) in India has not been discussed. Aim: To fill the above-mentioned void, we planned this study to determine the prevalence and degree of antibacterial resistance in GABHS isolates. Settings and Design: Children with acute pharyngo-tonsillitis who had not received antibiotic in the preceding week, attending the pediatric OPD, were prospectively enrolled over a period of 1 year. Throat swabs were collected from each child and transported to microbiology laboratory, as early as possible. Materials and Methods: A throat swab culture for GABHS was done. All GABHS were subjected to antibiotic susceptibility and minimum inhibitory concentration (MIC) test according to Clinical Laboratory Standard Institute (CLSI) guidelines. Results: In the present study, 12.6% (55/435) of the children with acute pharyngo-tonsillitis had throat swab culture positive for GABHS. The prevalence of macrolide resistance was 10.2%. The MIC50 for macrolide-resistant strain was 0.5 microg/mL (range, 0.125-8 microg/mL), and MIC90 was 8 microg/mL (range, 0.125-8 microg/mL). Tetracycline and co-trimoxazole resistances were 24.5% and 12.2% respectively. The values of MIC50 for tetracycline- and co-trimoxazole-resistant strains were 4 microg/mL (range, 0.125-32 microg/mL) and 2 microg/mL (range, 0.25-8 microg/mL) respectively. All isolates were sensitive to penicillin G and chloramphenicol on disc diffusion test. However, their MIC50 was 0.032 microg/mL (range, 0.012-0.125 microg/mL) and 2 microg/mL (range, 0.25-4 microg/mL) respectively. Conclusion: High prevalence of antimicrobial resistance found among GABHS needs a longitudinal surveillance of isolates from different centers in India.

Antimicrobial prescription patterns for common acute infections in some rural & urban health facilities of India.

BACKGROUND & OBJECTIVES: Irrational use of antimicrobials is a key factor behind rapidly spreading antimicrobial resistance in microorganisms. This study was undertaken to determine the rate and pattern of antimicrobial prescribing in patients with uncomplicated acute respiratory infections, fever and diarrhoea attending a few rural and urban health settings. METHODS: The study was done in primary and secondary health care facilities of public/government and private settings at four sites in India. Patients with fever, cough, diarrhoea or ear, nose or throat infections of < 7 days were included. Pregnant women, lactating mothers, infants, seriously ill patients and patients with bloody diarrhoea or purulent nasal or ear discharge were excluded. RESULTS: Overall antimicrobial prescription rate was 69.4 per cent (95% CI 67.1, 71.7). Wide variation was observed (Thiruvananthapuram 47.6%, Lucknow 81.8%, Chennai 73.1% and Vellore 76.5%). Physicians practicing in rural and public/government settings prescribed antimicrobials more frequently than those in urban and private settings (83.8, 81.9, 68.3 and 68.2% respectively). Antimicrobials were more frequently prescribed for patients presenting with fever. Highest rate was noticed for children aged between 6 and 18 yr. Patients of the high-income group received antimicrobials more frequently (72.7%). In both public/ government and private settings, for patients who purchased medicines, the rate was higher (82.4 and 68.9% respectively), vs. those receiving free medicines (70.2 and 46.2% respectively). Two third of all antimicrobials prescribed were penicillins and co-trimoxazole, and > 40 per cent of prescriptions from private sector were quinolones and cephalosporins. INTERPRETATION & CONCLUSIONS: Our findings showed that prescription of antimicrobials for acute respiratory infections and diarrhoea was extremely common and warrants interventional strategies.

Descriptive epidemiology of dengue transmission in Uttar Pradesh.

We report epidemiology of dengue infection as revealed through a hospital based surveillance for dengue infection over a 3 year period in Lucknow, U.P., India. In 2003-2005, children with acute febrile encephalopathy (AFE) and in 2005-2006, children with acute undifferentiated febrile illness (AUFI) were enrolled. IgM antibodies to dengue were tested by ELISA in acute serum. A total of 118/563 (20.9%) patients tested positive for dengue antibodies. Dengue transmission occurred round the year in the Lucknow region with peak in postmonsoon season and occurred equally in rural and urban areas. All the surrounding districts were affected, with no distinct high prevalence areas.

Aseptic meningitis: diagnosis and management.

The term aseptic meningitis encompasses all types of inflammations of the brain meninges other than that caused by pus producing organisms. It is usually a benign illness. Etiology of aseptic meningitis is very wide and includes many infections - both viral and non viral, drugs, malignancy and systemic illness. The most common cause is viral infection and enteroviruses - Coxsackie and ECHO viruses account for more than half of all cases. Clinical manifestations include headache, fever, malaise, photophobia and meningeal signs. Convulsions, neurological deficits and severe obtundation are rare except with certain non viral infectious meningitis. Diagnostic work up includes blood and cerebrospinal fluid (CSF) examination and serology for infectious meningitis. The polymerase chain reaction is a rapid and accurate method for detection of microbial DNA in CSF. Treatment is mainly supportive, except for the nonviral infectious etiology.

Protective role of BCG vaccination against tuberculous meningitis in Indian children: a reappraisal.

BACKGROUND: The protective role of BCG vaccination against tuberculous meningitis (TBM) is still controversial in India, largely due to the presence of other predisposing factors such as age, nutritional and socioeconomic status, and household contact. Very few Indian studies have focused on the interaction between BCG and these factors on the occurrence of TBM. METHODS: We did an unmatched hospital-based case-control study with prospective enrolment. Children with TBM diagnosed on the basis of predefined criteria were enrolled as cases. For each case, two children admitted on the same day and who did not have any neurological symptoms were enrolled as controls. Demographic data and information on predisposing factors for tuberculosis were collected for both cases and controls and the presence of a BCG scar was charted. Cases and controls were compared by univariate followed by multivariate analysis to obtain significant independent predictors for the occurrence of TBM. To assess the interaction between other predisposing factors and protective efficacy of BCG, a stratified analysis was also done. RESULTS: A total of 91 cases and 182 controls were enrolled over a one-year study period, of which 37 cases and 111 controls had a BCG scar. The crude odds ratio for the occurrence of TBM in the absence of a BCG scar was 2.28 (range: 1.32-3.94). The time elapsed since vaccination was significantly longer in the cases. Also, the proportion with a household contact was significantly higher in the cases, the mean age of the cases was higher than that of the controls, and the mean weight and height for age percentage were significantly lower. The cases had a significantly lower socioeconomic status. On multivariate analysis, the significant independent predictors for the occurrence of TBM were positive household contact with tuberculosis (adjusted OR 4.26; 95% CCI 2.26-8.04), absent BCG scar (adjusted OR 1.98; 95%ClI 1.09-3.57) and rural residence (adjusted OR 2.07; 95% ClI 1.02-4.17). CONCLUSION: Vaccination with BCG was found to be protective even after controlling for the effect of other variables. Stratified analysis showed that protection due to BCG failed to reach significance for those > 5 years of age, if the weight was <6 0% of that expected for age, in the presence of a household contact with tuberculosis, and in socioeconomic classes III, IV and V.