Sriram Krishnamurthy

Scrub typhus in children at a tertiary hospital in southern India: Clinical profile and complications

OBJECTIVE To study the clinical profile of and complications in children with scrub typhus. DESIGN Prospective observational study. SETTING Tertiary care hospital. METHODS Children up to 12 years of age who had a fever for more than five days without an identifiable infection were included. All children who were suspected of having rickettsial infections were defined as having scrub typhus if they had a positive Weil-Felix test result (OX-K 1:80 or more) and one or more of the following clinical features (after exclusion of other diagnoses): rash, edema, hepatosplenomegaly, lymphadenopathy, an eschar, and a tick bite or tick exposure. RESULTS Thirty-five children were diagnosed with scrub typhus between February 2010 and February 2011. The age of the patients ranged from 1.5 to 12 years. Edema, crackles/rhonchi, hepatomegaly and hypotension were encountered in 60%, 23%, 91% and 34% of patients, respectively. An eschar was observed in 11% of the cases. Complications included myocarditis with cardiogenic shock in 34% of the cases and acute kidney injury in 20% of the cases. Anicteric hepatitis and thrombocytopenia were observed in 31% and 61% of cases, respectively. One patient died. CONCLUSIONS High incidences of myocarditis and acute kidney injury were observed, which indicates that the children were treated at a late stage of the disease. Clinicians should be cognizant that myocarditis and acute kidney injury are serious manifestations of pediatric scrub typhus.

Early versus late enteral prophylactic iron supplementation in preterm very low birth weight infants: a randomised controlled trial

Objectives To evaluate whether preterm very low birth weight (VLBW) infants receiving early iron (EI) supplementation (2 mg/kg/day elemental iron) at 2 weeks postnatal age have improved serum ferritin levels compared with late iron (LI) supplementation at 6 weeks postnatal age. Design Single-blinded parallel-group interventional randomised controlled trial. Setting Tertiary care centre in southern India. Interventions Randomised at 2 weeks postnatal age to EI and LI groups and evaluated at 2, 6 and 12 weeks postnatal age. Outcome The primary outcome was serum ferritin level at 12 weeks, and the secondary outcomes were the incidence of neonatal morbidities, haemoglobin level, anthropometric parameters and blood transfusion requirements. Results Of the 104 babies randomised, outcomes were analysed in 46 and 47 babies in EI and LI groups, respectively. Serum ferritin level was significantly higher (p<0.001) at 12 weeks (82±5 vs 63±3 ng/mL) in the EI group. Haemoglobin (10.1±0.4 vs 9.2±0.4 g/dL) and mean corpuscular haemoglobin concentration (31±0.5 vs 29.4±0.5 g/dL) were also significantly (p<0.001) higher at 12 weeks in the EI group. There was a significant decrease of ferritin in the LI group and significant increase in ferritin in the EI group at 6 weeks compared with 2 weeks. There were no significant differences in the incidences of neonatal morbidities (necrotising enterocolitis, periventricular leukomalacia, retinopathy of prematurity), anthropometric parameters and blood transfusion requirements between the two groups. Conclusions EI supplementation in preterm VLBW infants improves serum ferritin and haemoglobin levels. Trial registration: CTRI/2013/01/003277.

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study.

Background: Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world. Objectives: The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years. Materials and Methods: In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded. Results: The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI. Conclusions: Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.

Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial

Objective To assess the efficacy of combined use of scorpion antivenom (SAV) with prazosin, compared with prazosin alone in children with Mesobuthus tamulus scorpion envenomation. Study design Randomised controlled trial. Setting A tertiary care hospital in south India. Patients 50 children with definite history and/or systemic manifestations of scorpion envenomation were recruited from the paediatric emergency or outpatient department from February 2012 to July 2013. Interventions The children were randomised into two groups. In 25 children, SAV was administrated as a slow intravenous bolus combined with prazosin (group A). Others received prazosin alone (group B). Results were analysed by Student t test and χ2 test. Main outcome measures Time required for resolution of autonomic symptoms, total dose of prazosin, adverse events. Results Children in group A recovered earlier than those in group B (mean difference 9.1 h, 95% CI 6.0 to 12.2). 23 children (92%) in group A were clear of autonomic symptoms within 10 h, compared with 10 children (40%) in group B (mean difference 52%, 95% CI 29% to 75%). The proportion of children deteriorating to clinical grade 3 or 4 was 8% in group A as against 44% in group B (p<0.01). The mean dose of prazosin required was 54 µg/kg versus 130.8 µg/kg in group A and B, respectively (p<0.01). SAV was not associated with severe adverse reactions. Conclusions Usage of SAV led to faster recovery and reduced the incidence of myocardial dysfunction. Combined therapy with SAV and prazosin is beneficial for children with M tamulus scorpion envenomation. Trial registration number: CTRI/2013/09/004002 (Clinical Trials Registry of India).

Fanconi–Bickel syndrome in a 3-year-old Indian boy with a novel mutation in the GLUT2 gene

Fanconi–Bickel syndrome is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction and impaired utilization of glucose and galactose. Most cases have been reported from Europe, Japan, Turkey and the Mediterranean belt. We report a 3-year-old boy from southern India who presented with doll-like facies, florid rickets, massive hepatomegaly, growth retardation, renomegaly and laboratory evidence of proximal renal tubular dysfunction. Liver biopsy demonstrated evidence of glycogenosis. Direct sequencing of genomic DNA confirmed a diagnosis of Fanconi–Bickel syndrome, revealing a G-to-A substitution at position −1 of the splicing acceptor site in intron 1 of the GLUT2 gene in a homozygous pattern (c.16-1G>A or IVS1-1G>A). This novel mutation has not been described in earlier studies. The child was treated with oral potassium citrate, oral phosphorus supplementation, and alpha-calcitriol, on which metabolic derangements were corrected.

Profile of urinary tract infections in paediatric patients

Background & objectives: This cross-sectional study was conducted at a tertiary care centre in Puducherry, south India, with the aim of finding the profile of the paediatric urinary tract infection (UTI), bacterial pathogens involved, and also to observe vesicoureteric reflux (VUR) and renal scarring in these patients. Methods: A total of 524 paediatric patients ≤13 yr, suspected to have UTI, were included in the study. Urine samples were collected, processed for uropathogen isolation and antibiotic susceptibility test was performed as per the Clinical and Laboratory Standards Institute (CLSI) guidelines. Thirty two culture proven children with UTI underwent micturating cysto-urethrography (MCU) and dimercaptosuccinic acid (DMSA) scanning was done for 69 children. Results: of the 524 children, 186 (35.4%) had culture proven UTI with 105 (56.4%) being infants, 50 (27.4%) between 1-5 yr, 30 (16.12%) between 5-13 yr and 129 (69.35%) males. Posterior urethral valve (PUV) was noted in three, hydronephrosis in one, VUR in 18 and renal scarring in 33. VUR as well as renal scarring were more in males >1 yr of age. A significant association (P=0.0054) was noted with a combined sensitivity and specificity of these investigations being 83 and 90 per cent, respectively of the MCU and DMSA scans for detecting VUR. Escherichia coli was the most common pathogen isolated, sensitive to nitrofurantoin, followed by cefoperazone-sulbactam, aminoglycosides and meropenem. Interpretation & conclusions: Our results indicate that UTI varies with age and gender and extensive evaluation is required in boys under one year of age with UTI. This study also highlights the better efficacy of aminoglycosides, cefoperazone-sulbactam and nitrofurantoin in vitro compared with meropenem in Gram–negative uropathogens.

Systemic Lupus Erythematosus: Recent Concepts in Genomics, Pathogenetic Mechanisms, and Therapies

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder associated with multiple immunological abnormalities and a wide range of clinical manifestations. Recent progress in genetics has expanded the number of the genes associated with SLE to more than 20 in number and has contributed to improvement of understanding of the pathogenesis of the disease. This has enhanced the development of novel therapeutic targets and biomarkers for individualized and tailor-made clinical management of lupus patients. Despite this knowledge, however, it is a challenge to fully understand the genetic pathogenesis of the disease. The present paper describes the current concepts in the mechanisms, genomics, and pathogenesis of SLE and their implications for management of the disorder. The potential role of gene therapy, biological agents, intravenous immunoglobulin, anti-inflammatory cytokines, and cytokine inhibitors is discussed.

Arrhythmogenic Dilated Cardiomyopathy Due to a Novel Mutation in the Desmoplakin Gene

The authors describe an 11-year-old girl who presented with congestive heart failure due to arrhythmogenic dilated cardiomyopathy. She had curly, woolly hair since birth and palmoplantar keratoderma. Molecular genetic analysis of the desmoplakin gene revealed that she was homozygous for the c.3901C>T (p.Gln1301X) change in exon 23 of the desmoplakin (DSP) gene, confirming the diagnosis of Carvajal disease. As per the Arrhythmogenic Right Ventricular Dysplasia/ Cardiomyopathy Genetic Variants Database, this is a novel mutation. She was managed with diuretics, enalapril, carvedilol and amiodarone, is presently stable, and on regular follow-up. Carvajal disease is a rare cardiocutaneous disorder and few cases have been reported in the literature. The authors review the published cases of the Naxos-Carvajal phenotype from India. Pediatricians need to be aware of this clinical entity whenever arrhythmogenic dilated cardiomyopathy is associated with woolly hair and/or palmoplantar keratoderma.

Taken to Health Care Provider or Not, Under-Five Children Die of Preventable Causes: Findings from Cross-Sectional Survey and Social Autopsy in Rural India.

Background: Under-five children in India continue to die from causes that can either be treated or prevented. The data regarding causes of death, community care-seeking practices, and events prior to death are needed to guide and refine health policies for achieving national goals and targets. Materials and Methods: A cross-sectional survey covering rural areas of 16 districts from eight states across India was conducted to understand the causes of deaths and the health-seeking patterns of caregivers prior to the death of such children. Mothers of the deceased children were interviewed. The physician review process was used to assign cause of death. The qualitative data were analyzed as per standard methods, while STATA version 10 was used for analysis of quantitative data. Findings: A total of 1,488 death histories were captured through verbal autopsy. Neonatal etiologies, acute respiratory infection (ARI), and diarrhea accounted for approximately 63.1% of all deaths in the under-five age group. The causes of death in neonates showed that birth asphyxia, prematurity, and neonatal infections contributed to more than 67.5% of all neonatal deaths, while in children aged 29 days to 59 months, ARI and diarrhea accounted for 54.3% of deaths. Care providers of 52.6% of the neonates and 21.7% of infants and under-five children did not seek any medical care before the death of the child. Substantial delays in seeking care occurred at home and during transit. For those who received medical care, there was an apparent amongst in their caregivers toward private health providers. Conclusion: The deaths of neonates and postneonates taken to any health facilities highlight the need for providing equitable and high-quality health services in India. The findings could be used for policy planning and program refinement in India.

Acitretin‐Responsive Ichthyosis in Chanarin–Dorfman Syndrome with a Novel Mutation in the ABHD5/CGI‐58 Gene

Chanarin–Dorfman syndrome (CDS) is a rare nonlysosomal neutral lipid storage disorder characterized by congenital ichthyosis, lipid vacuoles in leukocytes (Jordans anomaly), and hepatomegaly. The authors herein report an 18‐month‐old boy with ichthyosis and hepatomegaly diagnosed with CDS and confirmed to have a novel c.506–3C>G mutation in the ABHD5/CGI‐58 gene. Our case also illustrates that retinoids such as acitretin could be useful in the treatment of skin manifestations in CDS even in the presence of liver derangement.