Non-Respiratory and Non-Diarrheal Causes of Acute Febrile Illnesses in Children Requiring Hospitalization in a Tertiary Care Hospital in North India: A Prospective Study.

Acute febrile illnesses (AFIs) in children from the developing world can have varying etiologies. Awareness of local epidemiology helps in prioritizing investigations and empiric treatment. This prospective study was carried out in a tertiary care center in North India, aiming to determine the burden, etiology, and outcome of AFI other than pneumonia and diarrhea in hospitalized children. A total of 613 consecutive children aged 3 months to 12 years with febrile illness of < 7 days during four selected months of 2014 representing different seasons were screened for eligibility. Those with acute respiratory diseases (N = 175, 28.5%) and diarrheal illness (N = 46, 7.5%) were excluded and 217 children were enrolled. Mean (standard deviation) age was 4.8 (3.4) years. Nearly half (N = 91, 41.9%) presented in post-monsoon season. Diagnosis could be established in 187 (86.2%) children. Acute central nervous system infections were the most common (N = 54, 24.8%). Among specific infections, scrub typhus was the most frequent (N = 23, 10.5%) followed by malaria (N = 14, 6.4%), typhoid (N = 14, 6.5%), and viral hepatitis (N = 13, 6.0%). Blood culture had a low (6.5%) yield; Salmonella typhi (N = 6) and Staphylococcus aureus (N = 5) were the common isolates. Serological tests were helpful in 50 (23%) cases. In multivariate analysis, hepatomegaly and/or splenomegaly independently predicted scrub typhus. Mortality rate was 10.1%. We conclude that AFI other than pneumonia and diarrhea are a significant burden and follow a seasonal trend. Scrub typhus has emerged as an important etiology of childhood AFIs in northern India. Periodic review of regional epidemiology will help in understanding the changing pattern of infectious diseases.

Defect of cobalamin intracellular metabolism presenting as diabetic ketoacidosis: a rare manifestation.

Hypoglycemia is the usual feature of commonly occurring organic acidemias. Organic acidemias manifesting as hyperglycemia or diabetic ketoacidosis are rare and only a few cases have been reported. We report a 13-month-old boy who presented with vomiting, dehydration, coma, hyperglycemia, high anion gap metabolic acidosis and ketosis, mimicking diabetic ketoacidosis (DKA). Treatment with parenteral fluid, electrolytes, and insulin infusion resulted in an improvement in hyperglycemia, but persistence of metabolic acidosis and lack of improvement of neurologic status led us to suspect an organic acidemia. Urinary organic acid analysis revealed increased methylmalonic acid levels. In addition, hyperhomocysteinemia and homocystinuria were also noted in presence of normal vitamin B12 levels. This confirmed the diagnosis of cobalamin metabolism defect leading to combined methylmalonic aciduria and homocystinuria. There was some improvement in neurologic status and metabolic parameters after treatment with low-protein diet, vitamin B12, folic acid, and L-carnitine, but he ultimately succumbed to polymicrobial nosocomial sepsis. The entire MMACHC gene of the patient was sequenced and no mutations were identified. This is probably the first case report of cobalamin intracellular metabolism defect (CblC/CblD/CblF/CblJ or ABCD4) presenting as diabetic ketoacidosis.

Recombinant human granulocyte colony-stimulating factor in preterm neonates with sepsis and relative neutropenia: a randomized, single-blind, non-placebo-controlled trial.

We performed a prospective, randomized, single-blind, non-placebo-controlled trial on preterm (<37 weeks) neonates (birth weight <2000g) with sepsis and absolute neutrophil counts (ANC) <5000 cells mm(-3) to study the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on all-cause-neonatal mortality and hematological parameters (total leucocyte (TLC, ANC, absolute monocyte and absolute platelet counts). The rhG-CSF group (n = 20) received 10 µg/kg/day of intravenous infusion of rhG-CSF once daily for 5 days along with conventional therapy, and the control group (n = 20) received conventional therapy alone. Hematological parameters on Days 0, 1, 3, 5, 7 and 14 of study entry and all-cause mortality rates at discharge were recorded. Baseline characteristics between the rhG-CSF and control group including mean birth weight (1395 ± 289 vs. 1500 ± 231g), mean gestational age (31.5 ± 2.68 vs. 32.6 ± 2.23 weeks), initial neonatal complaints and maternal characteristics were comparable. Mortality rates were significantly less among the rhG-CSF group (3/20 (15%) vs. 7/20 (35%), p < 0.05). By Day 5 (for TLC) and Day 3 (for ANC) of start of the intervention, rhG-CSF group had significantly higher TLC (8189 ± 1570 vs. 6936 ± 1128 cells mm(-3), p < 0.05) and ANC (4756 ± 1089 vs. 4213 ± 354 cells mm(-3), p < 0.05) compared to controls. ANC levels recovered to levels >5000 cells mm(-3) faster in the rhG-CSF group, with 80% babies having ANC >5000 cells mm(-3) by Day 7 of study entry compared with 35% in the control group (p < 0.05). Preterm neonates with sepsis and neutropenia treated with rhG-CSF adjunctive therapy have decreased all-cause mortality at discharge and a quicker recovery of their total leucocyte and ANC.

Rickets: a cause of delayed walking in toddlers.

OBJECTIVE: Children with complaints of not able to walk were investigated for rickets by appropriate history, clinical examination, serum biochemistry and radiology. METHODS: Children more than 1 yr were included. Each child was evaluated keeping in mind the possible causes of delayed walking. Also each child was thoroughly examined and diagnosed by combination of clinical, radiological, biochemical findings and response to treatment. RESULTS: Out of forty-two non-walkers during the study period, 25 patients turned out to be affected by nutritional rickets (60%). On follow-up at 3 weeks of treatment, all 25 patients (100%) showed radiological and biochemical response. Five patients were lost to follow-up after 3 weeks of treatment. Seventeen patients started walking within 3 months of treatment. Two patients did not start walking even after complete biochemical and radiological resolution. Radiological resolution, with limiting factor being the healing of lower end of ulna, averaged 5 months. CONCLUSION: The study reveals that majority of ricketic non-walkers start walking within 2 to 5 months of appropriate treatment.

Factors associated with treatment failure in childhood tuberculosis.

We retrospectively reviewed records of 541 children (315 boys) suffering from tuberculosis, median age 95 (range 2-180) months, to determine factors associated with treatment failure. 256 (47.3%) children had pulmonary tuberculosis (PTB) while 285 (52.7%) had extrapulmonary tuberculosis (EPTB). 459 (84.8%) children were cured and 82 (15.5%) had treatment failure. On bivariate analysis, AFB positivity [OR= 2.13 (95% CI 1.18- 3.85)], non-receipt of BCG vaccination during infancy [OR=1.73 (1.02- 2.91)] and EPTB [1.9 (1.16- 3.11)] were associated with treatment failure. On multivariate analysis, only extrapulmonary tuberculosis was significantly associated with treatment failure.

Assessment of inhalation technique and determinants of incorrect performance among children with asthma.

The objective of our study was to evaluate the pressurized metered dose inhaler (pMDI) with holding chamber technique of asthmatic children attending out patient pediatric chest clinic and determine factors associated with incorrect technique. All patients had previously received instructions regarding inhalation technique. The inhalation technique was assessed on a five-point checklist, four of which were considered essential. Two hundred and thirteen children (mean +/- SD age, 7.3 +/- 3.8 years; 151 boys) completed the study. Children were using their inhaler for a median duration of 6 months (range 1-96 months). One hundred and eighty-eight patients (88.3%) performed all essential steps correctly. The commonest mistake among the essential steps was not shaking the inhaler (n = 21, 9.9%) followed by inability to make a tight seal around the mouthpiece of the holding chamber (n = 12, 5.6%). Correct technique was not affected by gender, asthma severity and socio-economic indices: education level of parents, percapita monthly income, rural or urban background. Our study indicates that a large majority of children from a developing country setting, irrespective of lower education and income levels can be successfully educated to appropriately use inhalation device. Inhalation performance is not affected by socio-economic background of the patients. Comprehensive inhalation instructions and monitoring at each visit are however critical to ensure reliable and consistent performance of correct technique among asthmatic children.

Montelukast in pediatric asthma management.

Leukotriene modifiers (receptor antagonist and biosynthesis inhibitor) represent the first mediator specific therapeutic option for asthma. Montelukast, a leukotriene receptor antagonist is the only such agent approved for use in pediatric patients. Montelukast modifies action of leukotrienes, which are the most potent bronchoconstrictors, by blocking Cysteinyl leukotriene receptors. Systemic drug like mountelukast can reach lower airways and improves the peripheral functions which play a crucial role in the evolution of asthma. Review of existing literature showed that montelukast compared to placebo has proven clinical efficacy in better control of day time asthma symptoms, percentage of symptom free days, need for rescue drugs and improvement in FEV 1. Studies also demonstrated improvement in airway inflammation as indicated by reduction in fractional exhaled nitric oxide, a marker of inflammation. Studies comparing low dose inhaled corticosteroids (ICS) with montelukast are limited in children and conclude that it is not superior to ICS. For moderate to severe persistent asthma, montelukast has been compared with long acting beta agonists (LABA) as an add-on therapy to ICS, montelukast was less efficacious and less cost-effective. It has beneficial effects in exercise induced asthma and aspirin-sensitive asthma. Montelukast has onset of action within one hour. Patient satisfaction and compliance was better with montelukast than inhaled anti-inflammatory agents due to oral, once a day administration. The recommended doses of montelukast in asthma are- children 1-5 years: 4 mg chewable tablet, children 6-14 years: 5mg chewable tablet, ADULTS: 10mg tablet; administered once daily. The drug is well tolerated. Based on the presently available data montelukast may be an alternative treatment for mild persistent asthma as monotherapy where ICS cannot be administered. It is also an alternative to LABA as an add-on therapy to ICS for moderate to severe persistent asthma. The other indications for use of montelukast include: allergic rhinitis, exercise induced bronchoconstriction and aspirin-induced asthma.

Age-related clinical and microbiological characteristics of enteric fever in India.

A retrospective, hospital-based study at Safdarjang Hospital, India, was undertaken between January 1999 and December 2003 to estimate age-related epidemiological, clinical and microbiological characteristics in enteric fever cases. A total of 750 blood-culture-proven cases of enteric fever were studied. The majority of cases occurred in children aged 5-12 years and 24.8% of cases were in children up to 5 years of age. Salmonella serotypes showed an age-related predilection, with paratyphoid fever more common in adults. Classically-described clinical features of the disease were comparable among patients under and above 5 years of age. Hepatomegaly, anaemia and complications in general were more frequent in children up to 5 years of age. The antimicrobial resistance pattern, irrespective of Salmonella serotype, did not reveal a statistically significant difference across age groups for the different antibiotics tested. Multidrug resistance was seen only in Salmonella enterica serotype Typhi but not in S. Paratyphi A isolates. However, resistance to nalidixic acid was comparable in both serotypes. Age-related differences of serotype isolation rates, clinical presentation and associated complications are noteworthy for better case management and policy planning. More epidemiological studies regarding reasons for age-related differential serotype patterns would enable and guide public health strategies to contain enteric fever in endemic locations.

Current perspectives of enteric fever: a hospital-based study from India.

UNLABELLED: The last two decades have seen a change in the pattern of enteric fever with the emergence of multidrug-resistant strains (MDRS), particularly strains resistant to nalidixic acid. AIM: The aim of the study was to undertake a retrospective analysis of blood culture-confirmed cases of enteric fever diagnosed at Safdarjang Hospital, New Delhi, India from January 2001 to December 2003. METHODS: The epidemiological details, clinical features, treatment outcome and antimicrobial resistance patterns were studied. RESULTS: Of 377 blood culture-positive cases, 80.6% were Salmonella typhi and 19.4% Salmonella paratyphi A; 21.7% were children aged under 5 years and 6.1% were under 2 years. A significant decline in MDRS was observed, from 21.9% in 2001 to 12.4% in 2003 (p=0.04). There was a significant increase in nalidixic acid-resistant Salmonella (NARS) from 56.9% in 2001 to 88.9% in 2003 (p=0.0001). Complete resistance to ciprofloxacin (MIC>4 microg/ml) was detected in only two isolates, both Salmonella paratyphi A. Minimal inhibitory concentrations (MICs) of ciprofloxacin for NARS were increased (0.125-0.5 microg/ml) but were within National Committee for Clinical Laboratory Standards susceptibility ranges. NARS had a significantly longer fever defervescence time (7.7 vs 4.7 days, p<0.001) and hospital stay (12.1 vs 8.2 days, p<0.001), and higher rates of complications (55.5% vs 24.0%, p=0.014) and mortality than nalidixic acid-sensitive Salmonella (NASS). The rate of isolation of MDRS was higher in NARS than NASS (18.8% vs 7.3%, p=0.013). CONCLUSION: The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.

Idiopathic myelofibrosis with generalized periostitis in a 4-year-old girl.

Idiopathic myelofibrosis, a chronic myeloproliferative disorder of unknown origin, is characterized by splenomegaly, extramedullary hematopoiesis, leukoerythroblastosis, teardrop erythrocytes, and myelofibrosis. It is a rare disorder in childhood. The authors describe a 4-year-old girl with features consistent with idiopathic myelofibrosis, who also had generalized solid laminated periosteal reaction involving all long bones. The presence of thrombocytopenia at the onset and lack of leukocytosis were in contrast to the reported features seen in children. Recent case reports describe a relatively indolent course in children. Spontaneous remissions have also been described in pediatric cases. The fulminant course of this patient without any features of malignant transformation was noteworthy in this regard.

Congenital Langerhans cell histiocytosis: the self-healing variety.

Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare variant of Langerhans cell histiocytosis, presenting at birth or in the neonatal period with cutaneous lesions that involute spontaneously. Affected infants are otherwise well with no systemic illness. A case of CSHLCH, probably the first case report from India, is described. The patient presented on the third day of life with multiple papulonodular lesions over the body, with no systemic involvement. The lesions spontaneously regressed by 6 months of age, with no evidence of relapse at 1 year of age. Although CSHLCH is a benign and self-limited condition, long-term follow-up for evidence of relapse is emphasized.

Effects of peroxynitrite on pig coronary artery smooth muscle.

We examined the effects of peroxynitrite pretreatment of pig coronary arteries on their sarcoplasmic reticulum (SR) Ca(2+) pump function. Pretreating rings from de-endothelialized arteries with peroxynitrite, followed by a wash to remove this agent, led to a decrease in the force of contraction produced in response to the SR Ca(2+) pump inhibitor cyclopiazonic acid (CPA, IC(50) = 87 +/- 6 microM). Inclusion of catalase and superoxide dismutase with the peroxynitrite did not alter its effect indicating that the inhibition was produced by peroxynitrite. Contractions produced by 30 mM KCl were not affected by up to 250 microM peroxynitrite. Smooth muscle cells cultured from this artery gave a transient increase in cytosolic Ca(2+) in response to CPA. Treating the cells with peroxynitrite inhibited this increase. Treating the SR-enriched isolated subcellular membrane fraction with peroxynitrite produced an inhibition of the ATP-dependent azide-insensitive oxalate-stimulated Ca(2+) uptake. Thus, peroxynitrite damages the SR Ca(2+)pump in the coronary artery, and this inhibition appears to lead to an inability of the arteries to respond to CPA. Thus, peroxynitrite produced from superoxide and NO in the arteries may compromise regulation of coronary tone which requires mobilization of Ca(2+) from the SR.

Effects of free radicals on coronary artery.

Coronary arteries supply blood to the heart and hence the control of coronary tone is pivotal to human survival. Reactive oxygen species (ROS) in specified amounts play an important role in normal metabolic and signalling processes. However, excess ROS can cause severe cardiovascular damage. For example, NO is produced by endothelium as a signal for relaxation. However, in an inflammatory response, NO from endothelium or macrophages can combine with superoxide to produce more deleterious peroxynitrite. Excess ROS have been associated with loss of coronary artery pliability--loss of contraction in some instances and relaxation in others. Atherosclerosis may also be considered an inflammatory response that leads to artery blockage, coronary disease and ischaemia-reperfusion. ROS produce various types of damage to ion channels and pumps and this damage is associated with vascular diseases such as atherosclerosis and hypertension. Endothelium and smooth muscle in the coronary artery are also affected differently by individual ROS. In fact, endothelium may act to protect the underlying smooth muscle against ROS. This review will give an overview of this field.