ANNALS OF INSTITUTE OF CHILD HEALTH CALCUTTA (Affiliated to West Bengal University of Health Sciences)

Editor in Chief : Editor : Maya Mukhopadhyay Jaydeep Choudhury

Chief Advisors Umasankar Sarkar S K Sharma S L Sarkar Apurba Ghosh

Advisors Parthapratim Gupta Dipankar Das Jaydeb Ray Sukanta Bhattacharyya Nupur Ganguly Sankar Sengupta Surupa Basu Sandipan Dhar

Circulation Secretaries Prabal Ch Niyogi Arunaloke Bhattacharyya

Published by Ritabrata Kundu, Hony. Secretary, ICH, Calcutta

Correspondence Maya Mukhopadhyay Professor and Ex.Additional Director Website : www.ichcalcutta.org, Email : [email protected]

For Private Circulation Only ANNALS C OF

  INSTITUTE OF CHILD HEALTH CALCUTTA

ISSN - 0300 - 533X  VOLUME 18  NUMBER 1  JANUARY - JUNE 2018

Editor in Chief : Maya Mukhopadhyay  Editor : Jaydeep Choudhury CONTENTS Editorial Maya Mukhopadhyay, Jaydeep Choudhury ...... 3 Pediatric Acute Lymphoblastic Leukemia: A Review Dipshikha Maiti ...... 7 In Hospital Malnutrition: Is It An Often Overlooked Problem? Subinita Hazra, Sukanta Bhattacharyya ...... 12 Nipah Virus – An Emerging Nazneen Ahmed, Nupur Ganguly, Priyankar Pal , Apurba Ghosh ...... 18 Updates on Febrile in Childhood Prabhas Prasun Giri ...... 26 Role of Antibiotics In Acute In Children Sarmistha Sinha ...... 31 A Few Skeletal Dysplasias Presenting to The OPD of Institute of Child Health Debasish Mukherjee ...... 35 A Simplified Approach to Hematuria in Children Rana Saha ...... 40 Oral Allergy Syndrome Indrani Roy ...... 45 Recommended Vaccinations for Asplenic and Hyposplenic Children Rina Ghosh ...... 49 Atopic Dermatitis – General Skin Care Practices Raghubir Banerjee ...... 53 Highlights of PCR Based Detection of Genetic Disorders and Pathogens Pranab Roy ...... 56 Diagnosis of : What’s New? Surupa Basu ...... 59 An Atypical Case of Enteric Subrata Chakraborty, Parthapratim Halder, Soham Mitra, Samiran Das, Tanmoy Khan...... 61 A Newborn with Vein of Galen Malformation Mallar Mukherjee, Deepa, Tania Khan ...... 63 Journal Scan Rajiv Sinha...... 68

2 Vol 18 No 1 January – JUNE 2018 Editorial Humans are the natural host of pneumococcus. It resides in the nasopharynx of humans and transmitted by respiratory droplets to other individuals. In most cases, pneumococcal carrier state is asymptomatic and subsequently it is cleared from the nasopharynx. The duration of carriage is age and serotype dependent1. In some individuals pneumococci may spread locally to cause otitis media, sinusitis or pneumonia. Sometimes it may cause systemic infections including bacteremia and and in rare cases, infections in remote foci, such as joints, bones and soft tissues. Among many virulence factors of , pneumococcal capsular polysaccharide is the most important. The polysaccharide capsule significantly increases the resistance of pneumococci to phagocytosis. Pneumococcal virulence also depends on several serotype- specific characteristics, such as the chemical composition and molecular size of the capsular polysaccharide. The serotypes vary in virulence depending on their ability to activate the alternative and classical complement pathway, to deposit and degrade the complement components on the capsule and to resist phagocytosis. They also differ in their ability to induce antibodies2. Occult bacteremia and sepsis Occult bacteremia is the presence of bacteria in the bloodstream of febrile children 3 to 36 months of age not having any apparent focus of infection and clinically does not appear to be toxic. It has been reported in upto 4% of febrile children in pre conjugate era3. The fate of bacteria depends on the immunocompetence of the host and virulence of the organism. In some children it may be the earliest sign of serious infection rather than a transient state which resolves spontaneously. Generally spontaneous resolution occurs in well appearing children. The severity of bacteremia is also related to the number of organisms in blood stream and also specific host defense. Sepsis is the systemic maladaptive response of the body to the invasion of normally sterile tissue by pathogenic or potentially pathogenic microorganisms. In other words, sepsis is an overwhelming inflammatory and coagulopathic response to a source of infection. Sepsis, if not recognized early, or treated properly and aggressively is often a lethal syndrome. Clinical features Clinical features depends on factors like age of the child, the strain of the offending microorganism, the underlying disease of the patient and duration of illness3. Thorough clinical assessment must include temperature recording, pulse rate, blood pressure, perfusion by capillary refill, respiration rate and pattern, mental status, level of consciousness and urine output4. Early sepsis – Typical features are fever and tachycardia. Respiration may be normal or mildly raised with irregular breathing pattern. Mental status and consciousness level are unaffected. Urine output may be mildly reduced reflecting mild dehydration.

Annals of ICH, Calcutta 3 Late sepsis – Hypothermia and tachycardia with persistent tachypnea and irregular respiration. Consciousness is depressed and there is marked reduction in urine output. Blood pressure may be unaltered until a very late stage of sepsis. Skin – Core temperature gradient should be measured with probes on toe and rectum. Skin-core temperature difference of > 3oC is a sensitive marker for severe shock. Capillary refill time prolonged beyond 2 seconds in normal room environment is a reliable marker for reduced skin perfusion (4). Impaired perfusion may be recognized by cold peripheries, poor capillary refill, tachypnea, tachycardia and oliguria, where urine output is less than 0.5 mL/kg. Investigations Blood count: WBC count exceeding 15000 cells/cmm in a 3 to 36 month old child with fever without focus of infection is an indication that the child is at risk for developing bacteremia5. Low peripheral WBC count also suggests septicemia and observed during episodes of overwhelming bacteremia. Initial neutropihilia may progress to neutropenia with advancing disease. Hemoglobin level may fall rapidly. Peripheral blood smear may reveal thrombocytopenia, fragmented RBC, Howell-Jolly bodies and it indicates progression to disseminated intravascular coagulation (DIC). Markers of sepsis: C-reactive protein (CRP) – It can rise many fold within 24 hours. It may remain elevated up to several days even after elimination of infectious focus. Procalcitonin (PCT) – In healthy individuals, levels of PCT are below 0.1 ng/mL. In patients with sepsis, PCT levels may increase many fold6. PCT concentrations exceeding 10 ng/mL usually occur in patients with organ failure remote to the site of infection7. Blood culture: Blood culture is the gold standard for diagnosis of septicemia(3, 4). It is recommended that a blood culture should be obtained in 3-36 month old child with fever higher than 39oC to 40oC and total WBC count greater than or equal to 15000 cells/cmm and without a specific focus of infection2. Supportive Management Resuscitation: Airway and breathing should be taken care of. A peripheral venous canulation should be done immediately (8). Followed by aggressive volume resuscitation with fluid boluses of cryatalloid, usually normal saline. The goal is to maintain mean arterial pressure 65 mmHg and central venous pressure between 8 and 12 mmHg. Fluid and electrolyte balance: Fluid balance should be addressed under the headings of restoration of intravascular

4 Vol 18 No 1 January – JUNE 2018 volume, maintenance of fluid and replacement of ongoing losses. Electrolyte and blood glucose should be measured at regular intervals and corrected accordingly. Cardiovascular support: Inotropic support should be started when there are signs of impaired perfusion that have not responded to initial measures of fluid resuscitation (4). Dopamine 2.5-5 µg/kg/min should be started as first line measures. Dobutamine 2.5 µg/kg/min may be added for further inotropic effect and increased up to 20 µg/kg/min while keeping dopamine at 5 µg/kg/min which is the optimum dose for maintaining renal perfusion. If hypotension persists despite adequate CVP dopamine can be increased in 2.5-5 µg/kg/min increments up to a maximum of 20 µg/kg/min. A third inotrope may be introduced in the form of adrenaline 0.1-1.0 µg/kg/min or isoprenaline 0.1-2.0 µg/kg/min while keeping dopamine at the renal dose of 5 µg/kg/min. Noradrenaline may be used as a fourth inotrope. Respiratory support: Early use of mechanical ventilation along with sedation and paralysis has many advantages. It removes the work of breathing thus it allows for redistribution of limited cardiac output to vital organs, hemodynamic monitoring becomes easier and the respiratory component of acid-base balance can be manipulated easily9. DIC: Many patients with septic shock show evidence of disseminated intravascular coagulation (DIC). Manifestations are deranged clotting studies, thrombocytopenia and raised fibrin degradation products. Management of DIC is mainly supportive along with correction of underlying cause. Children with severely deranged clotting studies should be transfused fresh frozen plasma or cryoprecipitate. Patients presenting with severe thrombocytopenia and active bleeding may require platelet transfusion. Low molecular weight heparin injection is an option in patients with severe coagulation derangement and impending peripheral gangrene10. Deep vein thrombosis (DVT) prophylaxis: Patients with septic shock syndrome are at high risk for development of DVT. They should be administered subcutaneous low molecular weight heparin. Mechanical DVT prophylaxis like intermittent compression device or graduated compression stockings may be used. Stress ulcer prevention: Patients with septic shock are prone to develop stress related mucosal bleeding. They should be given H2 receptor inhibitors. Blood product administration: The minimum target level hemoglobin is 7 to 9 gm/dl. After initial resuscitation, packed red blood cell or whole blood may be transfused if hemoglobin level is below 7 gm/dl. Antibiotic therapy: Along with appropriate resuscitation and supportive measures, optimal use of antibiotic

Annals of ICH, Calcutta 5 regimens is the critical determinant of survival in sepsis and septic shock. Antibiotics should be started early. Prevention of bacteremia11 (i) Education and training of healthcare workers. (ii) Hospital infection control policy. (iii) Hand hygiene. (iv) Appropriate barrier precautions during catheter insertion. (v) Adherence to aseptic catheter site care. (vi) Disinfection of injection ports before use. (vii) Using Teflon or polyurethane catheters. (viii)Using peripheral rather than central venous catheter when it is possible. (ix) Using subclavian rather than jugular insertion sites. (x) Removal of catheters as soon as possible. (xi) Replacement of tubings after blood products or lipid emulsions. (xii) Not to use topical antibiotic ointment on insertion sites, except using dialysis catheters.

1. Pelton S I, Jacobs M R. Pneumococcal infections. In: Cherry J D, Steinbach W J, Harrison G J, Hotez P J, Kaplan S L, editors. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th edn. Philadelphia: Elsevier Saunders 2014, pp 1198-246. 2. Klugman K P, Black S, Dagan R, Malley R, Whitney C G. Pneumococcal conjugate vaccine and pneumococcal common protein . In: Plotkin S A, Orenstein W A, Offit P A, editors. Vaccines, 6th edn. Philadelphia: Elsevier Saunders 2013, pp 504-412. 3. Kaplan S L, Valleje J G. Bacteremia and septic shock. In: Cherry J D, Steinbach W J, Harrison G J, Hotez P J, Kaplan S L, editors. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th edn. Philadelphia: Elsevier Saunders 2014, pp 824-36. 4. Choudhury J. Sepsis beyond neonatal period. In: Choudhury J, Kundu R, editors. Pediatric Infectious Diseases, 1st edn. New Delhi: Jaypee Brothers, 2012, pp 354-68. 5. Baraff L J, Bass J W, Fleisher G R, et al. Practic eguideline for the management of infants and children 0 to 36 months of age with fever without source. Pediatr 1993; 92: 1-12. 6 Assicot M, Gendrel D, Carsin H, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341:515–8. 7. Muller B, Becker KL, Schachinger H, et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000; 28: 977–83. 8. Savel R H, Gropper M A. Sepsis, sever sepsis syndrome, and septic shock. In: Parsons P E, Wiener- Kronish J P, editors. Critical Care Secrets, 4th edition. Philadelphia: Mosby Elsevier 2007, pp 205-13. 9. Butt W. Septic shock. Pediatr Clin North Am 2001; 48: 601-25. 10. Davies E G, Elliman D A C, Hart C A, Nicoll A, Rudd P T. Manual of Childhood Infections, 2nd edition. Philadelphia: W B Saunders, 2001. pp 14-52. 11. Wenzel R, Bearman G, Brewer T, Butzler J-P. A Guide to Infection control in the Hospital, 4th edition. Boston: International Society of Infectious Diseases, 2008. pp 170-2.

Dr Maya Mukhopadhyay, Editor-in-Chief Dr Jaydeep Choudhury, Editor

6 Vol 18 No 1 January – JUNE 2018 Pediatric Acute Lymphoblastic Leukemia: A Review Dipshikha Maiti Assistant Professor, Department of Pediatric Hematology, Institute of Child Health, Kolkata

Childhood cancer is being recognized as an cells within the. Presentation can be very important health concern globally. More than varied and nonspecific, with a combination 80% of the newly diagnosed cases of of constitutional symptoms and signs of bone childhood cancer are from the developing marrow failure (anemia, thrombocytopenia, world1. Over the last century, India has made leukopenia). Involvement of extramedullary great progress in reducing infection-related sites commonly occurs and can may result in childhood deaths in India. Similar results need lymphadenopathy, splenomegaly or to be replicated also in children with hepatomegaly (around 20% at presentation). malignancies. Leukemia is the most common CNS involvement at time of diagnosis occurs childhood cancer worldwide. In India in 5–8% of patients and present as cranial childhood leukemia has been reported to nerve deficits, or features of raised contribute to around 25- 40% of childhood intracranial pressure. Mediastinal mass with cancers. 60 to 85% of all leukemias reported superior mediastinal mass may be a presenting are acute lymphoblastic leukemia (ALL). There feature in case of T-ALL. are important differences in the biology of Diagnosis ALL in India as compared to the world with Diagnosis of acute leukemia is established by a higher proportion of T-Cell ALL (20-50% the presence of 25% or morelymphoblasts as compared to 10-20% in the developed in the bone marrow or peripheral blood. world), hypodiploidy and translocations Simultaneously bone marrow samples are t(1;19), t(9;22), and t(4;11), all of which studied for morphology, flow cytometry, contribute to a poorer prognosis of this Immunophenotyping and cytogenetic testing leukemia2-4. for confirming the diagnosis and proper risk Pathogenesis stratification. with CSF analysis is done to evaluate for CNS ALL is a malignant transformation leading to involvement. Suuspected testicular uncontrolled proliferation of lymphoid involvement would require confirmation by progenitor cells in the bone marrow, blood a ultrasound of the scrotum. and extramedullary sites. In the majority of children with ALL, it appears as a de novo Classification malignancy in otherwise previously healthy To begin with, ALL was classified as per the individuals. Clinical manifestations of ALL French American British (FAB) morphological reflect the bone marrow infiltration with criteria that divided ALL into 3 subtypes (L1, poorly differentiated, precursor lymphoid L2 and L3) based on various characteristics

Annals of ICH, Calcutta 7 like cell size, cytoplasm, nucleoli, puncture with the presence of leukemic blasts vacuolation.18 In 1997, the World Health on cytospin and greater than 5 leukocytes/ Organization proposed a composite µL, or clinical evidence of CNS involvement classification in incorporating morphology as (such as a cranial nerve palsy). Approximately well as cytogenetic profile of the leukemic 2% of boys with newly diagnosed ALL will blasts and identified three types of ALL: B present with testicular involvement. lymphoblastic, T lymphoblastic and Burkitt- Besides clinical features, cytogenetic 5 cell Leukemia . Later revised in 2008, Burkitt- abnormalities are being increasing recognized cell Leukemia was eliminated as it is no longer to have a significant role in risk stratification seen as a separate entity from Burkitt and also development of targeted therapy. Lymphoma, and B-lymphoblastic leukemia Favorable cytogenetic aberrations include high was divided into two subtypes: B-ALL with hyperdiploidy and the ETV6/RUNX1 recurrent genetic abnormalities and B-ALL translocation[t(12;21)]. High hyperdiploidy is not otherwise specified. B-ALL with recurrent defined as presence of 51 to 65 chromosomes genetic abnormalities. [table 1] per cell or a DNA index of greater than 1.16. Prognostic Factors And Risk Several unfavorable cytogenetic changes have Stratification: also been identified. One feature strongly Accurate assessment of prognosis and risk associated with poor outcome is hypodiploidy, stratification is central to the management of defined as fewer than 44 chromosomes or a ALL. Historically, age and white blood cell DNA index of less than 0.81. Additional count at presentation have been used to risk cytogenetic changes associated with higher-risk stratify patients. Sanctuary sites are ALL include BCR-ABL fusion of t(9;22), extramedullary sites that are difficult to known as the Philadelphia chromosome (seen penetrate with systemic chemotherapy, and in 3% of pediatric ALL), MLL (Mixed involvement of these sites at initial diagnosis Lineage Leukemia) ( rearrangements involving are also been considered a high-risk feature. 11q23 (seen in 5% of pediatric ALL, often Around 3% of patients will demonstrate overt infants and adolescents), and, most recently (CNS) disease at identified, intrachromosomal amplification of 6 diagnosis, defined either as a diagnostic lumbar chromosome 21 . Presence of the Philadelphia

8 Vol 18 No 1 January – JUNE 2018 chromosome, t(9;22) allows targeted therapy doxorubicin or daunorubicin) for the higher with tyrosine kinase inhibitors like Imatinib. risk groups. Remission induction is followed In addition to these features, the response to by consolidation, which aims to eradicate the the initial therapy has emerged as a powerful submicroscopic residual disease that remains prognostic predictor. Historically a complete after a complete remission is obtained. This remission has been defined as less than 5% phase of chemotherapy involves combinations detectable blasts on bone marrow of different chemotherapeutic agents to microscopic morphology at the end of maximize synergy and minimize drug induction. Induction failure is seen in resistance, often including agents not used in approximately 5% of children with newly the initial remission induction, such as diagnosed ALL and portends a very poor mercaptopurine, thioguanine, methotrexate, prognosis. Evaluation of the bone marrow cyclophosphamide, etoposide, and cytarabine. by microscopy is often relatively insensitive, Consolidation chemotherapy is further divided into variable number of and has been shown to be complemented chemotherapy cycles depending on the and, in part, displaced, by evaluation of protocol used and usually lasts between 6 to minimum residual disease (MRD). This 9 months in duration. Maintenance technique uses flow cytometry or the chemotherapy is the final, and longest, stage polymerase chain reaction (PCR) to assess for of treatment in childhood ALL. A much less disease at a significantly lower limit of intensive regimen than the prior detection (1 leukemic blast in 10,000–100,000 chemotherapy, the prolonged maintenance cells). Evaluation of bone marrow MRD at phase has been demonstrated to lower the the end of induction has proved to be an risk of relapse once remission has been independent factor predicting outcome, and established. It usually lasts at least 2 years. The has also been shown to be useful in the backbone of maintenance therapy is peripheral blood as early as day 8 of therapy7. antimetabolite therapy with methotrexate and Treatment of newly diagnosed acute mercaptopurine, both available in oral lymphoblastic leukemia formulations. The cornerstone of ALL therapy is reliance The fourth component of the treatment of on multidrug regimens to avoid development ALL is CNS directed therapy. This approach of resistance. Chemotherapy is administered includes both treatment of patients with clinical as blocks of have varying intensity depending CNS disease at diagnosis and prophylaxis for on the risk group of patients with increasingly patients with no CNS disease. Before the intensive regimens corresponding to more 1970s, ALL directed treatment protocol aggressive disease categories. The first block lacked this component. Although bone is the remission induction usually lasting marrow remission could be achieved using between 4 to 6 weeks in various protocols. systemic chemotherapy, most children The agents used during induction include eventually developed CNS relapse8. All vincristine, corticosteroids, and asparaginase, modern treatment plans include intrathecal with the addition of an anthracycline (usually administration of chemotherapy beginning

Annals of ICH, Calcutta 9 during remission induction. Some protocols Novel agents in the treatment of acute include intrathecal treatment throughout lymphoblastic leukemia: therapy, whereas others do not include it in Current efforts in advancing the treatment of maintenance. Options for intrathecal ALL focus on targeted immunotherapy and chemotherapy include including intrathecal personalized medicine which is a paradigm methotrexate or a combination of intrathecal methotrexate, cytarabine, and hydrocortisone shift from the nonspecific targeting of (known as triple intrathecal). Given the risk conventional chemotherapy. Immunotherapy of toxicity of cranial radiation, manifesting is a promising field that seeks to harness the primarily as intellectual disability (particularly power of the immune system to allow for a with younger patients) and as second more targeted approach towards leukemic malignant neoplasms, its utilization has been cells in order to reduce toxicities to normal progressively declining. Many protocols cells of the body. Chimeric antigen receptors reserve its use for only those at highest risk (CAR T) are one example of modified of CNS relapse while some institutions defer adoptive cell transfer whereby the patient’s its use altogether. For those patients with overt own cytotoxic T cells are genetically engineered CNS disease at presentation, several small to express an antibody to target leukemic studies have shown that by increasing the intensity of the intrathecal and systemic antigens (often CD19), often enhanced by the chemotherapy, cranial irradiation can also be inclusion of costimulatory binding regions deferred for these patients9,10. that allow for improved cytotoxicity and duration of cells12. Another example of The role of allogeneic hematopoietic stem cell transplant (HSCT) in first remission of ALL immunotherapy is blinatumomab, a bispecific is not yet well defined, and is a controversial anti-CD19/CD3 molecule, which enhances topic. Broadly speaking, HSCT is considered cytotoxic killing by binding both a protein for those patients with the very highest risk expressed on the leukemic blast (CD19) and of relapse and/or treatment failure, which has one expressed on autologous T cells (CD3)13. been most closely associated with those Another promising novel treatment strategy patients demonstrating hypodiploidy or focuses on the epigenetic changes seen in leuke- induction failure. General tenets of HSCT for mogenesis, with the use of histone deacetylase ALL include the use of total body irradiation inhibitors (HDACi), such as vorinot-stat14. (TBI) in the preparative regimen, and Finally, bortezomib is a proteasome inhibitor improved outcomes for patients who that interferes with natural killer ?B signaling undergo transplant after achieving MRD- negative disease status. The optimal donor has and is able to enhance bcl-2 and bcl-x, historically been a matched sibling, although rendering blasts more sensitive to apoptosis, advances with alternative donor sources are particularly in combination with conventional now also showing promise11. chemotherapy agents15.

1 0 Vol 18 No 1 January – JUNE 2018 References lymphoblastic leukemia and its relationship to 1. Dinshaw KA, Shastri SS, Kurkure AP, other prognostic factors: a Children’s Oncology Nandakumar A, editors. Cancer Awareness, Group study. Blood. 2008; 111(12):5477–85. Prevention and Control: Strategies for South 8. Evans AE, Gilbert ES, Zandstra R. The increasing Asia. Geneva: UICC Publications; 2006. incidence of central nervous system leukemia in 2. Magrath I, Shanta V, Advani S, Adde M, Arya children. (Children’s Cancer Study Group A). LS, Banavali S, et al . Treatment of acute Cancer. 1970; 26:404. lymphoblastic leukaemia in countries with 9. Pui CH, Campana D, Pei D, et al. Treating limited resources; lessons from use of a single childhood acute lymphoblastic leukemia protocol in India over a twenty year period. Eur without cranial irradiation. N Engl J Med. 2009; J Cancer 2005;41:1570-83. 360(26):2730–41. 3. Rajalekshmy KR, Abitha AR, Pramila R, 10. Sirvent N, Suciu S, Rialland X, et al. Prognostic Gnanasagar T, Maitreyan V, Shanta V. significance of the initial Immunophenotyping of acute lymphoblastic (CSF) involvement of children with acute leukaemia in Madras, India. Leuk Res lymphoblastic leukaemia (ALL) treated without 1994;18:183-90. cranial irradiation: results of European 4. Siraj AK, Kamat S, Gutiérrez MI, Banavali S, Organization for Research and Treatment of Timpson G, Sazawal S, et al . Frequencies of the Cancer (EORTC) Children Leukemia Group major subgroups of precursor B-cell acute study 58881. Eur J Cancer. 2011; 47(2):239–47. lymphoblastic leukemia in Indian children differ 11. Hochberg J, Khaled S, Forman SJ, et al. Criteria from the West. Leukemia 2003;17:1192-3. for and outcomes of allogeneic haematopoietic 5. Harris NL, Jaffe ES, Diebold J, Flandrin G, stem cell transplant in children, adolescents and Muller-Hermelink HK, Vardiman J et al. World young adults with acute lymphoblastic leukaemia Health Organization classification of neoplastic in first complete remission. Br J Haematol. 2013; diseases of the hematopoietic and lymphoid 161(1):27–42. tissues: report of the Clinical Advisory 12. Brentjens RJ, Curran KJ. Novel cellular therapies Committee meeting-Airlie House, Virginia, for leukemia: CAR-modified T cells targeted to November 1997. J Clin Oncol 1999; 17: 3835– the CD19 antigen. Hematology Am Soc 3849. Hematol Educ Program. 2012; 2012:143–51. 6. Heerema NA, Carroll AJ, Devidas M, et al. 13. Hoffman LM, Gore L. Blinatumomab, a Bi- Intrachromosomal amplification of Specific Anti-CD19/CD3 BiTE(®) antibody for chromosome 21 is associated with inferior the treatment of acute lymphoblastic leukemia: outcomes in children with acute lymphoblastic perspectives and current pediatric applications. leukemia treated in contemporary standard-risk Front Oncol. 2014; 4:63. children’s oncology group studies: a report from 14. Burke MJ, Bhatla T. Epigenetic modifications in the children’s oncology group. J Clin Oncol. 2013; pediatric acute lymphoblastic leukemia. Front 31(27):3397–402. Pediatr. 2014; 2:42. 7. Borowitz MJ, Devidas M, Hunger SP, et al. 15. Pui CH, Jeha S. New therapeutic strategies for Children’s Oncology Group. Clinical significance the treatment of acute lymphoblastic leukaemia. of minimal residual disease in childhood acute Nat Rev Drug Discov. 2007; 6:149–65.

Annals of ICH, Calcutta 11 In Hospital Malnutrition: Is It An Often Overlooked Problem? *Subinita Hazra, **Sukanta Bhattacharyya *Postgraduate, **Professor, Institute of Child Health, Kolkata

Abstract Poor nutrition is an under recognized cause of significant morbidity in hospitalized children. In addition to presenting with poor nutrition at the time of admission, children often suffer worsening of their nutritional status during the course of hospitalization, often due to under recognition of ongoing poor intake. Pediatric hospitals should provide adequate attention in recognizing and treating this common co- morbid condition. Keywords : Malnutrition, Hospitalized children

Introduction for age, weight for age, mid-upper arm Malnutrition is defined as a state in which a circumference, BMI) for the evaluation of the deficiency (or excess) of energy, protein, and nutritional status and there is no technique other nutrients causes measurable adverse which is not subject to criticism. The effects on the body and on growth (in Malnutrition Screening tool (MST) is a simple children), and may impact clinical outcome. three-question tool assessing recent weight and Although the term malnutrition includes both appetite loss1. Related to the MST, the over-nutrition (obesity) and undernutrition, in Malnutrition Universal Screening Tool this article we focus specifically on (MUST) was developed to detect both undernutrition. Undernutrition appears to be undernutrition and obesity1. Nutrition Risk an independent predictor of outcome and is Score (NRS), Pediatric Nutritional Risk Score associated with a higher rate of infectious and (PNRS), Screening Tool for the Assessment non-infectious complications, increased of Malnutrition in Pediatrics (STAMP), mortality, longer length of hospital stay and Subjective Global Nutritional Assessment increased hospital costs. It is associated with (SGNA), Pediatric Yorkhill Malnutrition Score altered physiological responses, increased (PYMS) and Screening Tool for Risk of resource utilization and influences outcome Impaired Nutritional Status and Growth during illness. Identifying alteration in the (STRONGkids) are a few common screening nutritional status in hospitalized children is tools for children admitted in hospital12. The fundamental for the early establishment of recommendation is that the one which is interventions, preventing the installation of better to detect the nutritional problem of undernourishment in risk situations or the population under study should be used. diminishing its severity when it is already The most often used measurements, weight present. There are several methods (viz. height and stature, are elemental in the assessment

1 2 Vol 18 No 1 January – JUNE 2018 of growth. The advantages of anthropometry children at risk of malnutrition.It can be are its low cost, its facility of execution and, considered thatas a result of the primary mainly, its universal use. disease for which the child is hospitalized, the Despite its high prevalence and consequences, , chemokines and mediators which medical awareness of malnutrition is lacking3,4. are formed shift the metabolism towards the Only a small fraction of hospitalized patients catabolic state or reduce the appetite with are assessed for nutritional status or referred insufficient calorie intake. Caloric deficit may for nutrition support. The term “nutritional also develop with an increase in loss or deterioration” has been used to describe decreased absorption from gastrointestinal significant weight loss in hospitalized children, system. a precursor to acute malnutrition. Careful Epidemiology and risk factors for nutritional evaluation at admission to the hospital-acquired malnutrition: hospitals is essential for identification of In 2016, 22.9%, or just under one in four children at risk for further nutritional children under age 5 worldwide had stunted deterioration and may allow interventions to growth. Between 2000 and 2016, stunting optimize nutrient intake with a potential for prevalence globally declined from 32.7% to improving outcomes. The rates of nutritional 22.9%. In 2016, about one in two stunted deterioration developing in hospitalized children lived in South Asia and one in three children are greater than in normal population in sub-Saharan Africa.In India, the prevalence due to the negative effect on the nutritional of stunting among under-five is 48% and status as a result of hospitalization. Although wasting is 19.8% and with an underweight this is known worldwide, in practice it is prevalence of 42.5%, it is the highest in the usually overlooked. world. Despite the existence of countless Nutritional requirement of a hospitalized studies in published literature on the patient is often overlooked as the primary worldwide prevalence of malnutrition in concern is to treat the disease for which the children, there is paucity of study so far in the patient is admitted5. Children have limited field of hospital acquired malnutrition. energy reserves and an increased energy Rocha et al.(2006)6evaluated the effects of requirement to cater for higher metabolic and hospitalization in 203 children under five years nutrient turnover rates when compared with of age, admitted to a public hospital in adults. Furthermore, they have increased Fortaleza, Brazil. Campanozziet al. described nutritional energy demands for growth and the problem of malnutrition in 496children development. The metabolic changes resulting admitted to a public hospital in Foggia, Italy from infectious processes or acute injuries lead with mildclinical conditions.They showed that to a metabolic response that deeply affects the number of childrenleaving the hospital the production, use and demand for nutrients malnourished, measured as z-scores below at cellular level. Thus, poor feeding in a sick 2SD, were higher than those at admission. child further increases unmet needs placing the Quadros et al. (2017)7 evaluated hospital

Annals of ICH, Calcutta 1 3 acquired malnutrition in children at a tertiary response to illness in children is not always care hospital in Kenya. Ferreira et al (2002)8 predictable, and varies in intensity and duration evaluated evolution of nutritional status in between individuals. The caloric burden hospitalized children at a teaching hospital at imposed by the metabolic response to injury, Alagoas, Brazil. The conclusion was Children surgery or may be proportional who remained in hospital for a longer period to the severity and duration of the stress but of time showed larger weight deficits, cannot be accurately estimated. Nutritional indicating that hospitalization did not support cannot reverse or prevent the contribute towards the improvement of their metabolic stress response. However, failure initial nutritional status. Kazem et al. (2011)8 to provide optimal calories and protein during evaluated the nutritional status of children the acute stage of illness could result in under five years of age, from admission to exaggeration of existing nutritional discharge, at Basrah Maternity and Child deficiencies or result in new onset malnutrition. Hospital in Southern Iraq. Esparza et al10. The large energy imbalances secondary to evaluated the risk of malnutrition of both under and overfeeding in critically ill hospitalized children in a University Public children must be avoided12. This requires an Hospital in Mexico. Oztruk et al.(2003)11 individualized nutritional regimen that must evaluated the effects of hospital stay on be tailored for each child and reviewed nutritional anthropometric data in Turkish regularly during the course of illness. children. The adverse effect of hospitalization The unique hormonal and profile on nutritional status was shown to be most manifested during critical illness is obvious on the 2–6-year age group with characterized by an elevation in serum levels undernourished children. They also found of insulin, glucagon, cortisol, catecholamines, reduced anthropometric parameters in all and proinflammatory cytokines13. Increased patients withmild malnutrition at admission serum counter-regulatory hormone (p < 0.05). concentrations induce insulin and growth Etiology of hospital acquired hormone resistance, resulting in the catabolism malnutrition of endogenous stores of protein, The etiology of malnutrition developing carbohydrate, and fat to provide essential during illness is multifactorial, and common substrate intermediates and energy necessary factors contributing to the protein and caloric to support the ongoing metabolic stress deficits during the hospital stay include; (A) response13,14. increased energy demands secondary to the In general, the net increase in muscle protein metabolic stress response, (B) failure to degradation, characteristic of the metabolic accurately estimate energy expenditure and (C) stress response, results in a large amount of inadequate substrate delivery at the bedside12. free amino acids in the circulation. Free amino (A) The metabolic stress response : acids are used as the building blocks for the The profound and stereotypic metabolic rapid synthesis of proteins that act as

1 4 Vol 18 No 1 January – JUNE 2018 inflammatory response mediators and are insensible fluid losses and transient absence of used for tissue repair. Remaining amino acids growth during the acute illness may predispose not used in this way, are channeled through some hospitalized children to the risk of the liver, where their carbon skeletons are overfeeding16. utilized to create glucose through (C) Nutrient intake at the bedside : gluconeogenesis. Although, the provision of Prescription and Delivery - Delay in initiation optimal dietary protein does not eliminate the of nutrition, suboptimal use of parenteral overall negative protein balance associated nutrition and overall failure to prescribe with the catabolic response to injury, it may adequate calories and protein are factors slow the rate of net protein loss14. responsible for malnutrition during hospital Carbohydrate turnover is simultaneously admission. increased during the metabolic response, with significant increase in glucose oxidation, and Besides drainage of calories that are essential gluconeogenesis15. However, the for normal growth in children, many illnesses administration of exogenous glucose does not also interfere with proper feeding through blunt the elevated rates of gluconeogenesis, anorexia, nausea or vomiting, thus and net protein catabolism continues predisposing to hospital-acquired unabated15. A combination of dietary glucose malnutrition. There is a further need to and protein may improve protein balance comply with hospital routines like scheduled during illness, primarily by enhancing protein times for meals and reduce interference by synthesis. The stress response is also clinical processes, namely ward rounds and characterized by increased rates of fatty acid diagnostic procedures which withhold oral oxidation. As seen with the other catabolic intake (nil by mouth) and compromise nutrient changes associated with stress response, the intake. Some drugs (e.g. Antibiotics) also cause provision of dietary glucose does not decrease anorexia, nausea and vomiting, or increase fatty acid turnover in times of illness. frequency of diarrhoea or constipation, leading to a reduction in food intake and/or (B) Estimation of energy requirement loss. In addition, failure to recognize during Illness : malnutrition, lack of screening tools and staff The metabolic alterations during critical illness to assist with feeding, failure to record daily may be dynamic and change during the course intake of patients and lack of nutritional of illness. The standard equations used for training for hospital staff can all contribute to estimating energy requirements may under-nutrition in hospitalized patients underestimate the resting energy expenditure Strategies for prevention of hospital- and lead to underfeeding. The failure to acquired malnutrition provide adequate calories during this phase may lead to the loss of critical lean body mass 1. Acknowledge the prevalence of and worsening of existing malnutrition. malnutrition in hospitalized children. However, decreased activity, decreased 2. Nutrition support integrated into the

Annals of ICH, Calcutta 1 5 primary healthcare team. further deteriorate during the course of illness. 3. Nutritional assessment and evaluation of Both macronutrient and micronutrient nutrition goals in all hospitalized children. malnutrition have been described. Assessment 4. Examine institutional barriers to nutrition of nutritional status on admission will allow support and implement practice change. identification of those children at high risk of further nutritional deterioration. A basic 5. Assessment of nutritional adequacy and understanding of the metabolic stress detection of nutritional deterioration with the help of regular anthropometric and response and accurate assessment of energy biochemical assessments during the expenditure are essential for designing hospital stay. individually tailored nutritional prescription for hospitalized children. Both underfeeding and 6. Early initiation and maintenance of Enteral Nutrition. overfeeding are common among hospitalized children and have significant impact on 7. Awareness of underfeeding, overfeeding outcomes from illness. Accurate measurement and micronutrient deficiencies. of energy expenditure, availability of nutrition 8. Aim for individually tailored nutritional support team, use of nutrition therapy regimen and serial assessment during the guidelines and protocol based assessment of course of hospital stay. nutritional parameters at admission and Conclusion regularly during hospital stay are some steps Malnutrition is prevalent in children admitted to improve the nutritional state of hospitalized to the hospital and their nutritional status may children.

Reference : ActaPediatrica, Volume102, Issue10, October 1. Lisa A. Barker, Belinda S. Gout, and Timothy 2013 ,Pages e460–e466 C. Crowe; hospital Malnutrition: Prevalence, 5. Nilesh M Mehta, Christopher P Duggan; Identification and Impact on Patients and the Nutritional Deficiencies during Critical Illness; healthcare system; 2009 Oct; 56(5): 1143-1160;doi: 10.1016/ 2. Huysentruyt K, et al. Nutrition. The j.pcl.2009.06.007, PediatrClin North Am STRONG(kids) nutritional screening tool in 6. Rocha GA, Edmundo JM, Mortins CV. The hospitalized children: a validation study; 2013 effect of hospitalization onnutritional status of Nov-Dec children.0021-7557/06/82-01/70, Jornal de 3. NerminKapçi, Mustafa Akçam, TugbaKoca, PediatriaCopyright © 2006 by SociedadeBrasileira SelimDereci, MücahitKapci; The nutritional de Pediatria. status of hospitalized children: Has this subject 7. Del-Rossi Sean Quadros, Rose Kamenwa, been overlooked? –Turk J Gastroenterol 2015; Samuel Akech& William MMacharia (2017): 26: 351-355 Hospital-acquired malnutrition in children at a 4. K Huysentruyt, P Aliet, L Muyshont, T tertiary care hospital, South African Journal of Devrekar, P Bontems, Y Vandenplas;Hospital- Clinical Nutrition related undernutrition in children: still an often 8. Haroldo S. Ferreira, Adijane O.S. França; unrecognized and undertreated problem- Evolution of nutritional status in hospitalized

1 6 Vol 18 No 1 January – JUNE 2018 children, Journal de Pediatra, 2002; 78(6): 461- critically ill children, Pediatric Lcu of the Hospital 466. 13. de Groof F, Joosten KF, Janssen JA, et al. Acute 9. Ahmed IbraheamKazem, Mea`adKadhum stress response in children with meningococcal Hassan, effect of hospitalization on the sepsis; important differences in the growth nutritional status of under 5 children, The hormone/insulin like growth factor I axis Medical Journal of Basrah University, Vol 29, between nonsurvivors and survivors. J No. 1&2, 2011 ClinEndocrinolMetab. 2002;87:3118-24. 10. Nelly Carolina Muñoz-Esparza, Edgar Manuel 14. Erin E. Shaughnessy, Lisa L. Kirkland, Vásquez-Garibay, Enrique Romero-Velarde and Malnutrition in Hospitalized Children: A Rogelio Troyo-Sanromán:Risk of malnutrition Responsibility and Opportunity for Pediatric of hospitalized children in a university public Hospitalists - Hospital Pediatrics, January 2016, hospital; Nutr Hosp. 2017; 34(1):41-50 ISSN Volume 6, Issue 1. 0212-1611 - CODEN NUHOEQ S.V.R. 318. 15. Cameron JW, Rosenthal A, Olson AD. 11. Ozturk Y, Buyukgebiz B, Arslan N, Ellidokuz Malnutrition in hospitalized children with H. Effects of hospital stay on nutritional congenital heart disease. Arch PediatrAdolesc anthropometric data in Turkish children. Med. 1995;149:1098-102. JTropPediatr. 2003; 49:189-90. 16. Hardy CM, Dwyer J, Snelling LK, Dallal GE, 12. doServidorPllblicoEstadual de Slio Paulo Adelson JW. Pitfalls in predicting resting energy “Francisco Morato de Oliveira” and Hospital, requirements in critically ill children; a comparison Slio Paulo – Universidade Federal de Slio Paulo, Escola Paulista de Jt. edicina – Slio Paulo, Brazil; of predictive methods to indirect Nutritional and metabolic assessment of calorimetry.NutrClinPract. 2002; 17:182-9.

The Trust Board of The Institute of Child Health, Calcutta Appeal for generous donation (Exempted under Section 80G of the Income Tax Act 1961) for the benefit of ailing Children of our Country ICH, Kolkata wants to Progress, Improve and Survive with your Support.

Annals of ICH, Calcutta 1 7 Nipah Virus – An Emerging Viral Disease *Nazneen Ahmed, **Nupur Ganguly, ***Priyankar Pal , ***Apurba Ghosh *MD PGT , **Associate Professor , ***Professor , Institute of Child Health, Kolkata

Introduction Genome and structure In recent decades, zoonotic pathogens have The Nipah virus is an enveloped, single induced considerable stress and anxiety in a stranded, negative sense RNA virus6-8. The broad range of societies worldwide. The genome of the Malaysia NiV is 18,246 nt in emergence of Nipah virus (NiV) in Peninsular length whereas it is 18,252 nt for the Malaysia in September 1998 was the second Bangladesh NiV. Infection studies in the in a series of spillover events. The first, starting African green monkeys indicated that the NiV- in September 1994, was an outbreak of BD is more pathogenic than the NiV-MY. This Hendra virus (HeV) in Brisbane, Australia. The explains why more cases in Bangladesh/India Malaysia epidemic resulted in 265 cases of have shorter incubation periods, more acute with 109 deaths and the respiratory symptoms, greater human-to- culling of 1.1 million pigs .Since 1998, human transmission and higher case fatality Malaysia and Singapore have not documented rates. human cases; however, human disease has Reservoir of the virus been continuously reported in Bangladesh Fruit bats of the genus Pteropus ,also known since 2001, with mortality rates estimated at as Indian flying fox ,have been identified as approximately 70%.A total of 36 outbreaks natural reservoirs of Nipah virus9-11. Evidence of NiV encephalitis were reported in of Nipah could be demonstrated in Bangladesh and India during 2001–2018 P.giganteus in Bangladesh and India. In including the recent outbreak in Kerala which addition to multiple species of bats, the virus has claimed 17 lives. can naturally infect pigs, horses, dogs, cats and Discovery and classification humans. Nipah virus has also been shown to experimentally infect guinea pigs, hamsters, In early March 1999, virologists from the ferrets, squirrel monkeys and African green University of Malaya had isolated this virus monkeys. This wide range of species tropism from cerebrospinal fluid of an encephalitis is due to the fact that it uses ephrin B2/B3 patient. The name “Nipah” virus was molecules as their entry receptors12-14. proposed because the first isolate was made 15 from clinical material from a fatal human case Modes of transmission from Kampung Sungai Nipah, a village in During the Malaysia outbreak ,direct contact Negeri Sembilan1-3. The virus belongs to the with sick pigs or their contaminated family Paramyxoviridae and genus tissues(respiratory droplets, throat and nasal Henipavirus4,5. secretions)was the major mode of

1 8 Vol 18 No 1 January – JUNE 2018 Fig 1A. Fruit bat aka Indian flying fox (Pteropus species) Fig 1B. Infra-red tracking of bats transmission.90% of the infected people were Case definitions22 pig farmers or had contact with pigs. During the outbreaks in Bangladesh and India , the Suspect Nipah case : Person from a disease got transmitted via consumption of community affected by a Nipah outbreak who fruits or fruit products(e.g. raw date palm juice) has: contaminated with urine, saliva, semen and • Fever with new onset of altered mental excreta of reservoir fruit bats. Person-to- status or seizure and/or Person transmission has also been reported among family and caregivers of patients. • Fever with headache and/or Incubation period15 : In humans range from • Fever with Cough or shortness of breath 4 days to 18 days, with more than 90% at 2 Probable Nipah case weeks or less. Suspect case – patient/s who resides in the 16-21 Pathogenesis : same village where confomed case- . patient/ Ingestion/Inhalation of large droplets s were living during the outbreak period and who died before complete diagnostic Virus resides in olfactory/respiratory epithelial specimens could be collected. cell , cranial nerve , cells of immune system OR and then enter draining lymph nodes Suspect case – patients who came in direct Viremia contact with confirmed case-patients in a hospital setting during the outbreak period and Small blood vessels and lymphatic vessels in who died before complete diagnostic different organs in the form of vasculopathy specimens could be collected. and vasculitis resulting in perivascular cellular Confirmed Nipah case infiltration,inflammation and necrosis Suspected case who has laboratory Lung (trachea), Brain and other lymphoid confirmation of Nipah virus infection either organs by:

Annals of ICH, Calcutta 1 9 • Nipah virus RNA identified by PCR from Japanese B encephalitis, falciparum malaria, respiratory secretions, urine, or HSV encephalitis, dengue hemorrhagic fever, cerebrospinal fluid. Isolation of Nipah scrub typhus. If NiV is suspected on the basis virus from respiratory secretions, urine or of epidemiologic history,exposure history, cerebrospi nal fluid. and/or clinical manifestations, infectious Clinical features disease specialists and the proper public health authorities, including the WHO,should be The clinical picture of a symptomatic Nipah notified immediately. Laboratory diagnosis of infected case comprises combinations of NiV is relatively straight forward but requires following symptoms : Moderate to high grade maximal containment (biosafety level 4). fever( usually persists for 5-7 days ), headache, Consequently, diagnostic samples should be vomiting, cough, breathlessness, changein collected with great caution and with use of behaviour/sensorium23,24, seizures/abnormal proper personal protective equipment and movement, myalgia, fatigue. Initially most strict barrier nursing techniques.The samples patients have normal blood pressure .With may be as follows : disease progression , there may be fall in blood pressure and oxygen saturation .Rashes, (a) Throat swab in viral transport medium hemorrhagic manifestations may be (b) Urine 10 ml in universal sterile container absent.The respiratory system and the nervous (c) Blood in plain vial (atleast 5ml) systems are most commonly affected. The (d) CSF (atleast 1 ml) in sterile container pulmonary manifestations include aspiration or ventilator associated pneumonia , pleural With adherence to established biosafety effusion ,atypical pneumonia with chest precautionary measures, samples should be radiograph showing diffuse interstitial safely packed in triple container packing and infiltrates and acute respiratory distress25,26. The should be transported under cold chain (2- CNS manifestations include reduced level of 6°C) to the testing laboratory with prior consciousness, seizure, , vasomotor intimation. Before dispatching the sample changes, cerebellar signs27, tremors, areflexia, disinfect the outer surface of container using hypotonia ,brainstem involvement in severe 1:100 dilution of bleach or 5% Lysol solution. cases , psychiatric features including depression Typical laboratory findings are leukopenia and personality changes28,29. Signs of meningeal (with cell counts as low as 1000/µL) with a irritation may be absent. The gastrointestinal left shift prior to leukocytosis, system involvement includes mild tender thrombocytopenia(with counts as low as hepatomegaly with ascites. 50,000/µL), increased concentrations of liver Diagnosis30-32 and pancreatic enzymes (aspartate aminotransferase > alanine aminotransferase, Nipah virus infections cannot be diagnosed  on the basis of clinical presentation alone. -glutamyltransferase, serum amylase). CSF Numerous diseases need to be considered in study may reveal pleocytosis with lymphocyte the of a febrile patient. predominance. MRI brain (Fig 2) may reveal The most important of the infectious diseases increased signal intensity over cortex , temporal 33,34 that closely mimic Nipah virus infection are lobe and pons . Definitive diagnosis include

2 0 Vol 18 No 1 January – JUNE 2018 Fig 2. MRI Brain showing features of acute Nipah virus infection including diffusion restriction on DWI Fig 3.Vasculitis and associated intravascular virus isolation attempts by cell culture35,36, RT- thromboisin brain necrosis , and peripheral PCR37,38 from bodily fluids(throat and nasal multinucleated giant cell formation swabs, CSF, urine, blood) or antibody reported months and even years after detection by ELISA(IgM and IgG)(currently exposure. done in National institute of Virology,Pune) Treatment Pathology39 Treatment of Nipah virus is entirely In autopsies performed on 32 Malaysian supportive because no accepted/approved, outbreak victims (29 full, 3 limited to the brain) efficacious, specific antiviral agents or vaccines pathological lesions were seen mainly in the are yet available. Supportive management brain with disseminated micro-infarction as a includes isolation, barrier nursing, resuscitation, result of vasculitis induced thrombosis and mechanical ventilation , oxygen inhalation, direct neuronal involvement(Fig 3). The nutritional support and fluid management. respiratory tract, heart and kidneys showed Symptomatic management include diffuse vasculitis as well.Medium sized and , ,treatment of small blood vessels appeared to be the most raised ICT, treatment of hypoglycemia and involved by NiV resulting in endothelial shock. Ribavirin , an antiviral drug , may multinucleated syncytia and fibrinoid necrosis. alleviate the symptoms of nausea, vomiting Complications and sequale40 and ,may have a role in reducing 20% of patients are left with seizure disorders mortality in patients of Nipah and personality changes while others had deficit encephalitis 41-42. A new drug called in attention, verbal and/or visual memory.A Favipiravir has recently been shown to be small number of people subsequently showed effective against Nipah viral infections in relapse or developed delayed-onset animal model43. encephalitis (>10 weeks of the initial exposure) Human Monoclonal antibodies developed by The longest delay in the onset encephalitis was Dr. Cristopher Broader of Queensland , 11 years. Latent infections with subsequent Australia , targeting the viral glycoproteins(anti- reactivation of NiV and death have also been G MAb or anti-F Mab) against Hendra and

Annals of ICH, Calcutta 2 1 Nipah have been shown since 2009 to be sap skirts).Freshly collected date palm juice highly effective for post-exposure protection should be boiled and fruits thoroughly washed on experimental animal. Its use in emergency and peeled before consumption. People setting is subject to approval of DCG. should avoid consuming half eaten fruits Prevention44-45 from the ground (Fig4A and 4B). Animal to human transmission can be reduced Human to human transmission can be prevented by washing hands for 20 seconds by use of gloves and other protective clothing after contact with a sick patient .There should should be worn while handling sick animals be use of proper barrier nursing techniques or their tissues and during slaughtering Use of injections and sharps should be limited. procedures. If an outbreak is suspected, the There should be safe waste disposal for animal premises should be quarantined

4A 4B Fig 4 : Measures to prevent animal to human transmission ; A – Slaughtering of pigs B - Keep fruit bats away from pigs , avoid half-eaten fruits, date palm sap immediately Culling of infected animals with potentially infected material including used close supervision of burial or incineration of PPE, linen, clothing of patient according to carcases.Restricting or banning the movement standard biomedical waste management of animals from infected farms to other areas. guidelines. No vaccine has been developed yet. The fruit bats should be kept away from pig. A number of recombinant vaccines like vaccinia ,canary ,HSV ,AAV are in the pipeline. Physical barriers to prevent bats from accessing A subunit vaccine using the Hendra G protein and contaminating sap e.g. cover sap collection (surface glycoprotein) produces cross reactive sites with protective coverings(e.g. Bamboo antibodies against HENV & NIPV46-47(Fig 5).

2 2 Vol 18 No 1 January – JUNE 2018 Fig 5. Measures to prevent Human to Human transmission

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2 4 Vol 18 No 1 January – JUNE 2018 33. Lim CCT, Sitoh YY, Hui F, et al. Nipah viral henipaviruses and other paramyxoviruses with encephalitis or Japanese encephalitis? - MR high potency. Antiviral Research. 144. 10.1016/ findings in a new zoonotic disease. Am J j.antiviral.2017.06.011. Neuroradiol 2000; 21(3):455-61. 42. Lo, Michael & C. Jordan, Paul & Stevens, Sarah 34. Schaefer PW, Grant PE, Gonzalez RG. Diffusion & Tam, Yuen & Deval, Jerome & T. Nichol, weighted MR imaging of the brain. Radiology Stuart & Spiropoulou, Christina. (2018). 2000; 217 (2):331-45 Susceptibility of paramyxoviruses and filoviruses 35. Kaku Y, Noguchi A, Marsh GA, Barr JA, to inhibition by 2'-monofluoro- and 2'-difluoro- Okutani A, Hotta K, Bazartseren B, Broder CC, 4'-azidocytidine analogs. Antiviral Research. 153. Yamada A, Inoue S, Wang LF. Antigens capture 10.1016/j.antiviral.2018.03.009. ELISA system for Henipaviruses using 43. E. Dawes, Brian & Kalveram, Birte & Ikegami, polyclonal antibodies obtained by DNA Tetsuro & Juelich, Terry & K. Smith, Jennifer & immunization. Arch Virol. 2012;157(8):1605– Zhang, Lihong & Park, Arnold & Lee, Benhur 1609. & Komeno, Takashi & Furuta, Yousuke & 36. Daniels P, Ksiazek T, Eaton BT. Laboratory Freiberg, Alexander. (2018). Favipiravir (T-705) diagnosis of Nipah and Hendra virus infections. protects against Nipah virus infection in the Microbes Infect. 2001;3:289–295 hamster model. Scientific Reports. 8. 10.1038/ s41598-018-25780-3. 37. Guillaume V, Lefeuvre A, Faure C, Marianneau P, Buckland R, Lam SK, Wild TF, Deubel V. 44. Ganguly, Subha & , Sunita & Kumar, Vikas & Specific detection of Nipah virus using real-time Pagrut, Nileshkumar & Kumari Faran, Neelam. RT-PCR (TaqMan) J Virol Methods. (2018). Nipah virus : an Update on Prevention 2004;120(2):229–237. and Control Strategies with Special Reference to the Latest Outbreak in India. International 38. Wacharapluesadee S, Hemachudha T. Duplex Journal of Veterinary Sciences and Animal nested RT-PCR for detection of Nipah virus Husbandry [AkiNik Publications, Rohini, RNA from urine specimens of bats. J Virol India]. 3. 20-21. Methods. 2007;141(1):97–101. doi: 10.1016/ j.jviromet.2006.11.023 45. Satterfield, Benjamin. (2017). The future of preventing and treating Nipah virus infection. 39. K. T. Wong and K. C. Ong, “Pathology of Acute Future Science OA. FSO220. 10.4155/fsoa-2017- Henipavirus Infection in Humans and 0056. Animals,” Pathology Research International, vol. 2011, Article ID 567248, 12 pages, 2011 46. C.C. BroderPassive immunization and active vaccination against Hendra and Nipah viruses 40. Tan CT, Goh KJ, Wong KT, et al.: Relapsed and Dev Biol, 135 (2013), pp. 125-138 late-onset Nipah encephalitis. Ann Neurol 2002; 51:703–708 47. C.C. Broder, T.W. Geisbert, K. Xu, D.B. Nikolov, L.F. Wang, D. Middleton, et al.Immunization 41. Lopez-Ona, Anne & He, Biao & T. Nichol, strategies against henipaviruses Curr Top Stuart & Spiropoulou, Christina & Lo, Michael. Microbiol Immunol, 359 (2012), pp. 197-223 (2017). 4'-Azidocytidine (R1479) inhibits

Annals of ICH, Calcutta 2 5 Updates on Febrile Seizure in Childhood Prabhas Prasun Giri Assistant Professor of Pediatrics and in Charge PICU, Institute of Child Health, Kolkata

Introduction (b) Focal in nature Febrile seizures (FS) are among the most (c) Reoccurs within 24 hours common reasons that patients present with iii. Febrile -A febrile seizure to pediatric emergencies. These seizures are lasting longer than 30 minutes. classically associated with high fever in children iv. Simple febrile seizure plus: Recurrent during their early lives . Scientists used to think simple febrile seizures within 24 hours. of FS as a benign condition, warranting Epidemiology nothing apart from reassurance. Over time, we have learned that the benign nature of FS Between 2% to 5% of neurologically healthy should be carefully rethought, as there are a infants and children experience at least 1 febrile number of atypical presentations with variable seizure in lifetime. The peak incidence is usually outcomes. in the second year of life. Seasonal variation with regard to seizure incidence has not yet Definition been fully understood. Studies have shown Febrile seizures are seizures that occur between that FS tend to occur more in the winter the age of 6 to 60 months with a temperature months and are more common in the evening. of 38 degree Celsius (100.4degree Farenehite) Simple febrile seizures do not have an increased or more , that are not the result of central risk of mortality ,where in some studies it has nervous system infection or any metabolic been shown that complex febrile seizures may imbalance, and that occur in the absence of a have an approximately 2 fold increase in the history of prior afebrile seizures. mortality as compared to general population. Classification Compared to age matched controls ,patients i. Simple febrile seizure/Typical febrile with febrile seizures do not have any increase seizure: It is primarily a generalised, usually in the incidence of abnormalities of tonic clonic seizure associated with fever, behaviour, scholastic performance, lasting for a maximum of 15 minutes and neurocognitive function or attention. not recurrent within a 24 hours period. Risk of first FS: ii. Complex febrile seizure/Atypical febrile Based on the previously mentioned causative seizures: It is characterised by one or more theories, several risk factors for developing of the following the first FS have been suggested. The degree (a) More prolonged(>15mins) of fever height is probably more relevant than

2 6 Vol 18 No 1 January – JUNE 2018 the degree of rise of temperature itself, Having 2 risk factors (2 major) caries a risk contrary to previous thought . A history of of recurrence 50-59% FS in a first-degree or higher relative seems 3 or more risk factors(at least 2 major)carries to be the factor with the strongest prediction a risk of recurrence upto 73-100% power . Other risk factors implicated in FS Genetic factors:Positive family history is found include preexisting developmental delays, day in many cases of febrile seizure. In some care attendance, stay in the neonatal nursery families,the disorder is inherited as an for more than 28 days, and various viral autosomal dominant trait and multiple single infections . Associations with childhood genes(FEB 1to FEB10). that cause the vaccinations and some mineral deficiencies, such as zinc and iron, remain unclear at the disorder have been identified in such families. moment. However the disorders appears to be polygenic in most of the cases. Risk of recurrent febrile seizures Risk of There are few risk factors presence of which can increase the subsequent episodes febrile Determining whether FS are able to convert seizures. The risk factors can be divided into to frank epilepsy has always been in the mind Major and Minor of pediatricians and researchers. In 1991,the first national population-based study came MAJOR from the UK and found no difference in the Age<1 year risk of subsequent epilepsy after simple FS Duration of fever <24 hours compared to the general population . In the Fever 38-39degree C(100.4 to 102.2F) late 1990s, studies revealed that that complex features of FS and a strong family history of MINOR epilepsy might carry a significantly higher risk Family history of febrile seizure of future epilepsy. Later, it had been found Family history of epilepsy that the presence of more than one risk Complex febrile seizure factor, especially a preexisting neurodevelopmental disease, a positive family Daycare history of epilepsy, or two or more complex Male gender features, may increase the epilepsy incidence Lower serum sodium at the time of fourfold . Although the risk factors for presentation recurrence of FS are quite different from anemia the risk factors of subsequent epilepsy, one interesting study found that the risk of Having no risk factors carries a risk of recurrence around 10 to 12% epilepsy may be slightly elevated with simple FS if they were very recurrent. The risk Having 1 risk factor (major) caries a risk of factors are shown in table 1. recurrence 25%-50% Almost any types of epilepsy can be preceded

Annals of ICH, Calcutta 2 7 Table 1. Risk factors for occurrence of subsequent epilepsy after a febrile seizure Risk Factors Risk Factors of Subsequent Epilepsy Simple febrile seizure 1% Recurrent febrile seizures 4% Complex febrile seizures 6% Fever <1 hour before febrile seizure 11% Family h/o epilepsy 18% Complex febrile seizure(focal) 29% Neurodevelopmental abnormalities 33% by febrile seizures and a few epilepsy Pediatric neurologists whether any blood syndromes that typically starts with febrile parameters except a capillary blood glucose seizures ,these are manly generalised epilepsy are at all needed to evaluate the case of typical with febrile seizures plus (GEFS+),severe or simple FS. Second and subsequent episodes of infany(Dravet of a typical FS does not need any syndrome), secondary investigations where first attack of typical FS to mesial temporal sclerosis. does not need any investigation form the Evaluation neurological point of view but sometimes During the evaluation of FS it is very much essential to identify the cause or source of important to confirm the diagnosis as febrile fever. Until it is obvious that the source of seizure and to exclude CNS infection like fever is a simple viral URTI some basic tests meningitis or encephalitis.The evaluation like a complete hemogram and CRP and compose of clinical examination and Malaria Parsasite and Dengue serology in the investigations. The following clinical features endemic areas should be done. Blood are more suggestive of a CNS infection than electrolytes is not routinely recommended simple FS. after a simple FS. These tests should be (a) A prolonged post ictal phase performed only when clinically indicated .A low sodium level is associated with higher risk (b) Recurrent seizures of recurrence of the FS within next 24 hours. (c) Onset of seizure after 24 hours of onset First episode of atypical FS needs further of fever. detailed evaluation including the blood for (d) presence of neck rigidity and a positive electrolyte and sometimes baseline liver kernig’s sign or brudginski’s sign. transaminases and Kidney function and arterial Among the investigations several laboratory blood gas. studies needs to be considered in evaluating Lumbar puncture : the patient with febrile seizure. CNS infection should be considered in Blood studies : differential diagnosis in FS especially in There is a debate among the Pediatricians and complex FS.Lumbar puncture should be

2 8 Vol 18 No 1 January – JUNE 2018 performed for all infants younger than 6 seizure.MRI is needed in some cases of months of age who present with fever and complex FS especially if the kid is seizure and if the child is ill appearing or at neurologically abnormal. any age there are clinical signs or symptoms Treatment of concern. A lumbar puncture is an option in a child of 6 to 12 months of age who is In general antiepileptic therapy, continuous or deficient in Haemphillus influenza type b and intermittent is not recommended for children streptocosccus pneumonia vaccination or for with 1 or more simple FS. Parents should be whom immunisation status is unknown. A counselled about the relative risks of lumbar puncture is always an option in kids recurrence of febrile seizures and recurrence who have been previously treated with of epilepsy. They should be educated about antibiotics.An EEG should therefore be the home treatment of acute seizure episodes restricted to special cases in which epilepsy is by nasal or buccal or rectal or rectal highly suspected, and generally it should be . Intermittent (oral used to delineate the type of epilepsy rather Diazepam 0.33mg/kg every 8 hours during than to predict its occurrence. At times if the fever or intermittent rectal Diazepam 0.5mg/ patient does not recover from a seizure then kg administered as a rectal suppository every an EEG can help distinguish between ongoing 8 hourly or oral Clonazepam 0.1mg/kg/day seizure activity and a prolonged posictal or Oral Clobazam .8 to 1.2mg/kg/day for 3 period, sometimes termed as nonepileptic twilight state. days ) are widely used as intermittent prophylaxis for FS. Such therapies help reduce, EEG : but do not eliminate the risks of recurrent There is no recommendation for routine EEG febrile seizures. Antipyretics can decrease the in case of first attack of typical febrile seizure. discomfort of the child but do not reduce Atypical febrile seizures should be evaluated the risk of having a recurrent FS, probably by an interictal EEG specially if the family because the seizures often occurs as the history of epilepsy is strong. temperature is rising or falling. Iron deficiency : is associated with an increased risk of FS and Neuroimgaing like CT or MRI is not thus screening for that and appropriate recommended in a case of simple febrile treatment is recommended.

References 1. S. Shinnar, “Febrile seizures and mesial temporal 2. R. J. Baumann and P. K. Duffner, “Treatment sclerosis,”Epilepsy Currents, vol. 3, pp. 115–118, of children with simple febrile seizures: the AAP 2003. J. H. Ellenberg and K. B. Nelson, “Febrile practice parameter,” Pediatric , vol. 23, seizures and later intellectual performance,” no. 1, pp. 11–17, 2000. Archives of Neurology, vol. 35, no. 1, pp. 17– 3. G. Capovilla, M. Mastrangelo, A. Romeo, and F. 21, 1978. Vigevano, “Recommendations for the

Annals of ICH, Calcutta 2 9 management of ‘febrile seizures’:Ad Hoc Task 9. R. C.Graves, K.Oehler, and L. E. Tingle, “Febrile Force of LICEGuidelinesCommission,” seizures: risks, evaluation, and prognosis,” Epilepsia, vol. 50, supplement 1, pp. 2–6, 2009. American Family Physician, vol. 85, no. 2, pp. 4. SteeringCommittee onQuality Improvement 149–153, 2012 andManagement and Subcommittee on Febrile 10. R. Mittal, “Recent advances in febrile seizures,” Seizures American Academy of Pediatrics, The Indian Journal of Pediatrics, vol. 81, no. 9, “Febrile seizures: clinical practice guideline for pp. 909–916, 2014. the long-term management of the child with 11. P. R. Camfield, C. S. Camfield, S.H. Shapiro, and simple febrile seizures,” Pediatrics, vol. 121, pp. C. Cummings, “The first febrile seizure- 1281–1286, 2008. instruction plus either 5. J. H.Menkes, Textbook of Child Enruology, or placebo to prevent recurrence,” The Journal Williams &Wilkins, 5th edition, 1997. of Pediatrics, vol. 97, no. 1, pp. 16–21, 1980. 6. S.Sisodiya, “Feverish prospects for seizure 12. A. Polizzi, G. Incorpora, P. Pavone et al., genetics,” Nature Genetics, vol. 46, no. 12, pp. “Generalised epilepsy with febrile seizures plus 1255–1256, 2014. (GEFS+): molecular analysis in a restricted area,” 7. A. T. Berg, “Are febrile seizures provoked by a Child’s Nervous System, vol. 28, no. 1, pp. 141– rapid rise in temperature?”TheAmericanJournal 145, 2012. of Diseases of Children, vol. 147, no. 10, pp. 1101–1103, 1993. 13. B. C. Lim, H. Hwang, H. Kim et al., “Epilepsy 8. L. C. Hampers and L. A. Spina, “Evaluation phenotype associated with a chromosome and management of pediatric febrile seizures in 2q24.3 deletion involving SCN1A: migrating the emergency department,” Emergency partial seizures of infancy or atypical dravet Medicine Clinics of North America, vol. 29, no. syndrome?” Epilepsy Research, vol. 109, no. 1, 1, pp. 83–93, 2011. pp. 34–39, 2015.

Nivedita School for Special Children

Since 1975 our special school is probably the only specific institutional centre in Kolkata that runs a school for special children and carries out regular academic, research and public awareness activities. It provides complete child psychiatric services through psychometry, pharmachotherapy, behaviour therapy, counseling, speech therapy etc, at inexpensive rates.

3 0 Vol 18 No 1 January – JUNE 2018 Role of Antibiotics In Acute Otitis Media In Children Sarmistha Sinha Consultant, Dept. of ENT, Institute of Child Health, Kolkata

Acute otitis media (AOM) is one of the leading factors and poor quality of air are the main causes of health care visits and drugs contributing factors. Children present with ear prescription, especially antibiotics in paediatric pain, especially when lying down, fever, pulling age group. As antibiotic resistance has become at an ear, difficulty in sleeping, crying or a global burden of the whole world, restriction irritable more than usual. Cold and cough, on its usage is urgently required. Inappropriate decreased hearing, dizziness and headache can use is one of the most important contributing be associated symptoms. Otoscopic factors for this resistance. Many countries have examination shows bulged or congested introduced clinical practice guidelines for tympanic membrane (TM) or new onset of AOM over the past decades to intoduce clear otorrhea not due to otitis externa2. The view about the mode of treatment. management should include antipyretics, AOM is an acute inflammation of the middle analgesics and antibiotics in some cases. ear caused by virus (such as influenza viruses, Management rhinovirus, adenoviruses and respiratory AOM is a self-limiting infection. Most children syncytial virus) or bacteria (such as S. get better within 3 days without antibiotics, pneumoniae, H. influenzae and M. catarrhalis). but it can last for up to 1 week. Complications This infection often results from cold, flu or such as mastoiditis are rare even without allergy which cause congestion and swelling antibiotics.3. of the nasal passages, throat and eustachian tubes. It is more common in children because Nowadays many western countries have made 4 of their narrower and more horizontal guidelines for the treatment of AOM . All of eustachian tubes which make them more them generally emphasise on the importance difficult to drain and more likely to get of accurate diagnosis, adequate analgesia, clogged easily. Adenoid can also be a symptomatic management and judicious and contributing factor as they are near to the selective antibiotic prescribing. opening of the eustachian tubes.Children have The Canadian Paediatric Society guidelines relatively larger adenoids and any suggest that all children younger than 2 years inflammation or enlargement of the adenoids of age with earache due to AOM and fever may block the tubes, thereby contributing to greater than 39°C be considered for treatment middle ear infection. with antibiotics5. In older normal children The estimated incidence of AOM is 11% and antibiotic administration is only recommended most of them occur in children younger than for those with perforated TM with purulent 5 years of age1. Harmful atmosphere, seasonal drainage or with middle-ear effusion with a

Annals of ICH, Calcutta 3 1 bulging TM , moderately or severely ill child UK (NICE 2008) with high fever [=39°C], moderate to severe no antibiotic or delayed antibiotics systemic illness, severe otalgia, those who have And/or antibiotics for severe cases, already been severely ill for 48 hours or there is any history of immunodeficiency, Bilateral AOM in children younger than 2 craniofacial abnormalities, tympanostomy years, AOM in children with otorrhoea tubes insertion or recurrent AOM. 4) Agence Française de Sécurité Sanitaire des For children who are alert, having mild otalgia Produits de Santé with mild or moderate bulging of the TM (AFSSAPS 2005) with low grade fever (<39°C) responding to antipyretics, watchful waiting can be advised. <2 years: antibiotics Antibiotics should be kept on hold .They are >2 years: watchful waiting unless indicated if symptoms worsen or do not symptoms are severe then use antibiotics improve in 24 to 48 hours2. And/or delayed treatment after re- Amoxicillin is the drug of choice given as 45 evaluation at 48-72 h to 60 mg/kg per day in 3 divided doses. If twice daily dose is considered, total daily doses 5) Guidelines of the German society for of 75 to 90 mg/kg per day are required. pediatric infectious diseases Amoxicillin-clavulanate should be considered (analgesia, nose if there is a history of amoxicillin use within drops) and watchful waiting for 24-72 h last month, concurrent purulent conjunctivitis if second look is assured. Antibiotics first or recurrent infection. Second or third line (amoxicillin) in severe disease, age<6 generation of cephalosporin can be used if months, risk factor allergic to penicillin . The duration should be According to the Italian Society of Preventive 10 days in children below 2 years or recurrent and Social Pediatrics (SIPPS), over-estimation AOM cases. Otherwise 5 day dose is adequate6. of AOM is responsible for inappropriate treatment, increased costs, adverse events as Guidelines of AOM well as spread of antibiotic resistance. They 1) American Academy of Pediatrics and provided five recommendations regarding American Academy of Family Physicians what not to do in AOM, such as (1) Do not (AAP/AAFP 2004) diagnose AOM without documenting middle Analgesia <2 years: antibiotics ear effusion (2) Do not diagnose AOM >2 years; watchful waiting without examining the entire tympanic 2) Scottish Intercollegiate Guidelines membrane; (3) Do not advise antibiotics Network (SIGN 2003) immediately in all cases of AOM (4) Do not administer ear analgesic drops without Analgesia examining the whole tympanic membrane (5) Delayed antibiotic treatment after 72 h Do not use macrolides routinely in the AOM 3) National Institute of Clinical Excellence, therapy7.

3 2 Vol 18 No 1 January – JUNE 2018 Present scenario vomiting are seen more commonly. Though Deinz Y et al8 showed that antibiotic In another study with Finnish children showed prescription rates decrease by 12% after that watchful waiting did not affect clinical implementation of clinical guidelines, condition, but it takes more time to return to antibiotics are routinely prescribed to children their regular activities which might have some with AOM in many centers. Percentage is as social and economic impact14. high as 80% even in USA9. Thompson et al showed that antibiotic usage for otitis media Conclusion : declined by 51% between 1995 and 2000.They Though anti-smoking campaigns, pneumo- also showed that though clinical guidance has coccal conjugate vaccination15 and strategies advocated limiting antibiotic prescribing for to promote breast- feeding 16 have reduced otitis media since 1997 in UK, general the incidence of AOM, it is still an important practitioners are not still strictly adherent to cause of clinic visit in paediatric age group 10 this . According to them decreased rate of and has significant socioeconomic impact. antibiotic usage is mainly due to diagnosis There is still poor adherence to clinical transfer. There is simultaneous decrease in guidelines due to many factors like fear of prescribing antibiotics for non-acute otitis serious complications and parental pressure. media and increase for acute otitis media .It is A more acceptable and easy to implement possibly to justify the decision to treat11. universal guideline is needed to avoid the 12 Cabral C et al tried to find out some reasons global threat of antibiotic resistance. for non adherence to the guidelines in their study on respiratory tract infection. Concerns Summary about the risk of the child becoming more ill • Children should be cared for when not prescribing antibiotics, missing a symptomatic relief rather than immediate diagnosis or parental pressure might result in antibiotics in AOM to assist in the fight injudicious use of antibiotics. This attitude is against antibiotic resistance, which is stated more common in young children. as the “greatest threat to health” by the Venekamp RP et al13, included thirteen World Health Organisation randomized controlled trials from high- • Acute complications from AOM such income countries with approximately 3400 as mastoiditis are rare with or without children receiving either antibiotics or placebo antibiotics in their study . No symptomatic improvement • Regular doses of or seen in first 24 hrs even with antibiotics. At 3 months, there is no difference in the number using the right dose for the age of children with abnormal tympanometry. or weight of the child at the right time to The incidence of complications such as be given. mastoiditis and meningitis were rare and not • Children with otorrhoea, who are different between two groups. Moreover systemically very unwell, have symptoms adverse effects of antibiotics, ie diarrhoea, and signs of a more serious illness or

Annals of ICH, Calcutta 3 3 with high-risk factors and children below • Close monitoring is needed. Parents are 2 years with infection in both ears are advised to seek medical help if symptoms more likely to be benefitted from worsen significantly, or the child becomes antibiotics systemically very unwell. References prescriptions: a systematic review.Arch Dis Child. 1) Monasta L, Ronfani L, Marchetti F, Montico M, 2018 Jun;103(6):597-602. doi: 10.1136/ Vecchi Brumatti L, Bavcar A, et al. Burden of archdischild-2017-314103. Epub 2018 Mar 3 disease caused by otitis media: systematic review 9) Grijalva CG, Nuorti JP, Griffin MR. Antibiotic and global estimates. PLoS One prescription rates for acute respiratory tract 2012;7(4):e36226). infections in US ambulatory settings. JAMA 2) Le Saux N, Robinson JL; Canadian Paediatric 2009;302:758–66. Society, Infectious Diseases and Immunization 10) Thompson PL, Gilbert RE, Long PF, Saxena S, Committee. Management of acute otitis media Sharland M, Wong IC .Has UK guidance affected in children six months of age and older. Paediatr general practitioner antibiotic prescribing for Child Health 2016;21(1):39-50. otitis media in children? J Public Health (Oxf). 3) Grossman Z, Zehavi Y, Leibovitz E, Grisaru- 2008 Dec;30(4):479-86. doi: 10.1093/pubmed/ Soen G, Shachor Meyouhas Y, Kassis I, et al. fdn072. Epub2008 Sep 1 Severe acute mastoiditis admission is not related 11) Lucas PJ, Cabral C, Hay AD, et al. A systematic to delayed antibiotic treatment for antecedent review of parent and clinician views and acute otitis media. Pediatr Infect Dis J perceptions that influence prescribing decisions 2016;35(2):162-5. in relation to acute childhood infections in 4) Ovnat Tamir S, Shemesh S, Oron Y, et al. Acute primary care. Scand J Prim Health Care otitis media guidelines in selected developed and 2015;33:11–20) developing countries: uniformity and diversity. 12) Cabral C, Lucas PJ, Ingram J, et al. "It’s safer to Arch Dis Child 2017;102:450–7. ..." parent consulting and clinician antibiotic 5) McWilliams CJ1, Goldman RD. Update on acute prescribing decisions for children with respiratory otitis media in children younger than 2 years of tract infections: An analysis across four qualitative age. Can Fam Physician. 2011 Nov;57(11):1283- studies. Soc Sci Med 2015;136-137:156–64. 5. 13) Venekamp RP, Sanders SL, Glasziou PP, Del Mar 6) Sakulchit T, Goldman RD Antibiotic therapy CB, Rovers MM. Antibiotics for acute otitis for children with acute otitis media.Can Fam media in children. Cochrane Database Syst Rev Physician. 2017 Sep;63(9):685-687 2015;(6):CD000219 7) Chiappini E, Bortone B, Doria M, Landi M, Di 14) Nitsche MP, Carreño M. Antibiotics for acute Mauro G, Marchisio P.What not to do in acute otitis media in children. Medwave 2015;15(Suppl otitis media: the top five recommendations 2):e6295 proposed by the Italian Society of Preventive 15) Fortanier AC, Venekamp RP, Boonacker CW, et and Social Pediatrics.Expert Rev Anti Infect Ther. al. Pneumococcal conjugate vaccines for 2017 Oct;15(10):897-902. doi: 10.1080/ preventing otitis media. Cochrane Database Syst 14787210.2017.1380518. Epub 2017 Sep 19. Rev 2014:CD001480. 8) Deniz Y, van Uum RT, de Hoog MLA, Schilder 16) Yilmaz G, Hizli S, Karacan C, et al. Effect of AGM, Damoiseaux RAMJ, Venekamp RP. passive smoking on growth and infection rates Impact of acute otitis media clinical practice of breast-fed and non-breast-fed infants. Pediatr guidelines on antibiotic and analgesic Int 2009;51:352–8.

3 4 Vol 18 No 1 January – JUNE 2018 A Few Skeletal Dysplasias Presenting to The OPD of Institute of Child Health Debasish Mukherjee Professor of Community Pediatrics, Special Interest in Radiology, Institute of Child Health, Kolkata Mild frontal prominenceThe skeletal C) Cystic bone dysplasias are a genetically and clinically Metatropic Dystrophy (Pic 2) heterogeneous group of disorders of skeletal This disorder is initially a short- limbed development and growth with an estimated dwarfism. Later due to vertebral anomalies prevalence of 1 in 4000 births. They can be divided into the osteodysplasias like and scoliosis it is transformed into a short- Osteogenesis Imperfecta and the trunk dwarfism. A characteristic feature is a chondrodysplasias like Metaphyseal Chondro- tail-likeappendage over the sacrum which is dysplasia. due either to an abnormally long coccyx or due to sacrococcygeal skin duplication. A few of the skeletal dysplasias which came to the outpatients department of Institute of Skull : May be normal or dolicocephalic Child Health are presented here. Thorax: Bell-shaped with short ribs which Oteogenesis Imperfecta (pic 1) skull and are spatulate anteriorly spine Long bones : Short with wide flaring of Skull: large vault with temporal bulge. the metaphyses which are 2 to 4 times wider presence of wormian bones than the diaphyses and dumb-bell shaped. The epiphyses are late-appearing and dysplastic. Vertebrae : flattened, later biconcave The femoral necks are short and there is Long bones : 3 types of long bones are hyperplasia of the greater trochanters. observed A) Thick bones with shortening Vertebrae : In infancy vertebrae are flat or and telescoping of fractures diamond-shaped They later become flat with B) Slender fragile bones with narrow shafts , anterior wedging. thin cortices and marked osteoporosis.

Pic 1 : Oteogenesis Imperfecta

Annals of ICH, Calcutta 3 5 Pic 2 : Metatropic Dystrophy Pelvis : Short iliac wings, horizontal acetabula, Skull : Brachycephaly late appearing capital femoral epiphyses Large anterior fontanelle may extend along Metaphyseal Chondrodysplasia – Schmid the metopic suture Type (Pic 3) Vertebrae: Small in size Clincally characterized by short stature, Occasionally short interpedicular distances of the vertebrae Thorax : Cupping of rib costochondral junctions with small cysts and wide anterior ends Premature fusion of sternal sutures gives rise to pigeon-breast deformity Pic 3 : Metaphyseal Chondrodysplasia – Schmid Limbs : Metaphyseal sclerosis and scalloping, Type sometimes with small cyst-like areas waddling gait and lumbar lordosis Dislocation or subluxation of radial head Skull: Normal Small hand bones Long bones : Ragged expanded cupped Occasional coxa vara metaphyses Femoral head may simulate Perthes Disease Normal epiphyses Disproportionately long fibula Spurs of bone extending from whole width of metaphyses into epiphyses Hips : Coxa vara Metaphyseal Chondrodysplasia- Type McCusick ( Cartilage Hair Hypoplasia) (pic 4) Clinically- Short stature , fine sparse hair,joint Pic 4 : Metaphyseal Chondrodysplasia- Type laxity McCusick ( Cartlage Hair Hypoplasia)

3 6 Vol 18 No 1 January – JUNE 2018 Multiple Epiphyseal Dysplasia (Pic 5) Clinically-- short limbs, rhizomelia,podgy Clinically : Present with short stature hands,short fingers with trident appearance bulging cranium, low nasal bridge,lumbar Hands and wrists :All epiphyseal centres of lordosis ossification late in appearing, small mottled, irregular Skull: large cranial vault with narrow base. Occasionally hydrocephalus Stumpy metacarpals Spine: vertebrae have short pedicles with Late ossifying carpals concave posterior borders, anterior wedginbg of the vertebrae at the thoracolumbar level, interpedicular distances of vertebrae decrease from above downwards. Thoracic cage : short ribs, scapulae cut off at the inferior angle. Pelvis; Square iliac wings, horizontal acetabula, narrow greater sciatic notch Pic 5 : Multiple Epiphyseal Dysplasia Long bones: short , thick, distal metaphyses Lower limbs: Epiphyses similar in appearance flared with V-shaped notch into which to upper extremities epiphyses fit. Proximal femur shows Femoral capital epiphyses involved but radiolucent oval area coxa valga actabulum spared Hypochondroplasia (pic 7) Vertebrae: Changes are minimal. Some Clinically : short stature,mild lumbar lordosis blurring of margins with flattening and irregularity maybe present Skull : mild frontal prominence Achondroplasia (Pic 6) Long bones: disproportionate femoral

Pic 6 : Achondroplasia

Annals of ICH, Calcutta 3 7 Pic 7 : Hypochondroplasia condyles, medial being larger than lateral, large Vertebrae: flattened with irregular margin greater trochanter of femur, large femoral Long bones: irregular metaphyseal margins head, long fibulae Hands: late appearing small carpal bones Spine: square - shaped lumbar vertebrae, short vertebral pedicles, non-increasing Pelvis: short iliac wings, acetabulum more interpedicular distances of vertebrae horizontal than normal with irregular margins, coxa vara Pelvis: horizontal acetabular roofs (Pic 10) Pseudoachondroplasia (Pic 8) Clinical – Hepatosplenomegaly , anaemia Clinical: short-limbed dwarfism Skull: thick sclerotic bone affecting both base Vertebrae: flat with tongue-shaped anterior and vault

Pic 8 : Pseudoachondroplasia projection from central part of vertebral bodies Long bones- metaphyses flared and irregular, epiphyses small and irregular Pelvis- irregular acetabular margins Spondylometaphyseal Dysplasia (Kozl- owski Type) (Pic 9) Clinically: shortlimbed dwarfism Pic 9 : Spondylometaphyseal Dysplasia (Kozlowski Type)

3 8 Vol 18 No 1 January – JUNE 2018 Pic 10 : Osteopetrosis Vertebrae: uniformly dense or sandwich or lesser density bands of greater or lesser appearance density bands of greater or lesser density Long bones: expanded club-shaped bands of greater or lesser density. metaphyses, epiphyses sclerotic and may show Phalanges and metacarpals: bone within bone dense centre surrounded by halo of dense appearance bone. Sometimes transverse bands of greater Pelvis: sometimes arcuate bands Quality Care At An Affordable Range Institute of Child Health proudly announces the presence of BLOOD BANK 4th Generation HIV testing, Malaria Antigen test, Blood Grouping and Cross Matching by gel technology and Component Separation An effort to serve the people in a better way. Both inhouse and outside services available

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Annals of ICH, Calcutta 3 9 A Simplified Approach to Hematuria in Children Rana Saha Consultant, Dept of Pediatric Nephrology, Institute Of Child Health, Kolkata

Introduction 3. Microscopic hematuria with clinical Hematuria is a common presenting symptom symptoms (fever, abdominal pain, of renal and urinary tract disorders in the oedema, rash) paediatric age group. Isolated microscopic 4. Asymptomatic microscopic hematuria hematuria is relatively common (0.5 - 4%) than with proteinuria macroscopic hematuria (less than 0.2%). It is Principal causes of hematuria defined as more than 5 RBC per high power Hematuria may originate from any part of field on microscopy. Dipstick positive can be the kidney and urinary tract. In paediatric age due to blood, haemoglobin or myoglobin. group, the source of bleeding is more often An absence of RBCs in the urine with a from glomeruli than from the urinary tract. A positive dipstick reaction suggests list of principal causes of hematuria is given hemoglobinuria or myoglobinuria (Table1). in Table 2. Table 1 Causes of red Urine Table 2 Principal causes of hematuria in Dipstick negative Dipstick positive children Haemoglobinuria • UTI – cystitis, pyelonephritis Chloroquine Myoglobinuria • Glomerular cause: Doxorubicin Post infectious GN (PIGN) Nitrofurantoin IgA nephropathy Rifampicin Haemolytic uremic syndrome (HUS) Food dyes SLE HSP Beets Others - ANCA positive glomerulonephritides Blackberries • Congenital anomalies of urinary system Metabolites • Calculi Bile pigments • Hypercalciuria Methemoglobin • Lower urinary tract causes Porphyrin Urethral trauma Tyrosinosis • Familial: Urates Thin basement disease, Alport’s syndrome Hematuria can be divided into following • Other rare causes Renal tumour groups: Acute interstitial nephritis 1. Macroscopic (gross) hematuria- Sickle cell disease Renal Tb 2. Isolated asymptomatic microscopic Coagulopathy hematuria (persistent if positive Drug induced - cyclophosphamide microscopy ×3 - 1 week apart)

4 0 Vol 18 No 1 January – JUNE 2018 Evaluation of a child with hematuria coloured urine with protenuria, RBC casts, and Evaluation of a child with macroscopic deformed (dysmorphic) RBCs in the urine. hematuria differs from that of asymptomatic An algorithm outlining the initial investigation microscopic hematuria. In most cases of of a child presenting with macroscopic macroscopic hematuria of glomerular origin hematuria and microscopic hematuria with is associated with smoky brown, tea or cola symptoms is shown in Fig1.

* look up table 1 ** Myoglobinuria (history of trauma/ high CK) and haemoglobinuria (high LDH) = discuss with the nephrologist *** consider other glomerular causes Fig.1 An algorithm outlining the initial investigation of a child presenting with macroscopic hematuria and microscopic hematuria with symptoms

Annals of ICH, Calcutta 4 1 Most children with isolated microscopic microscopic hematuria with protenuria. hematuria do not have a treatable or serious History and examination cause for hematuria and do not require an extensive evaluation. But, coexistent hematuria Once hematuria has been confirmed by and proteinuria signal the presence of positive dipstick and microscopy, one should significant renal disease. Fig 2 provides a concentrate to more specific aspects of the scheme for the evaluation of the child with history and physical examination.

Fig. 2. Scheme for the evaluation of the child with microscopic hematuria with proteinuria.

4 2 Vol 18 No 1 January – JUNE 2018 While eliciting history, note should be made genitalia to exclude local trauma. Examination o f of skin may identify a rash, and examination (1) Timing of hematuria in relation to of the joints may provide evidence of arthritis. micturition: Investigations (a) Initial (urethral) A child with gross hematuria should undergo (b) Total (kidney) prompt and comprehensive evaluation. History, physical examination and initial urine (c) Terminal (bladder) analysis usually identify if the source of (2) Incontinence,fever, dysuria, frequency or bleeding is glomerular or non glomerular. urgency – is suggestive of Urinary tract Investigations then can be tailored to specific infection ones to reach definitive diagnosis as described (3) Fever, exercise/ trauma/ bladder below: catheterisation/ menstruation –Transient (1) Urine dipstick: as sensitive as microscopy cause but leads to more false positive results (4) Flank pain, fever, dysuria – suggest acute (detects hemoglobinuria, myoglobinuria, pyelonephritis and hematuria) (5) Flank pain with radiation to groin may (2) Urine microscopy: fresh sample, necessary suggest obstruction (clot/ stone) after positive dipstick to confirm RBCs (6) Pharyngitis or impetigo / Upper (repeat if negative as could be false respiratory tract infection (URTI) negative/ intermittent) (a) Hematuria 2-3 weeks after URTI – (3) Urine culture and sensitivity consider post infectious (4) Urine protein:creatinine ratio - first sample glomerulonephritis of the day (b) Recurrent hematuria with URTI – (5) Urine Calcium: creatinine ratio – second suggest IgA nephropathy sample of the day ×3 (7) Family history – hearing loss, haematuria, (6) Renal tract USS stone, sickle cell trait, haemophilia, (7) FBC (and blood film if HUS suspected) chronic kidney disease (8) Renal profile (8) Drugs, food substances and toxins that (9) If glomerular cause suspected: give red urine (see Table 1) ASO and Anti DNase titre,Throat swab,C3 (9) Recurrent gross hematuria in young girl- and C4, ANA, ANCA, Anti-Double Stranded consider vaginal foreign body / abuse. DNA Physical examination is rarely useful in (10) Coagulation screen if history of bruises identifying the cause the hematuria, although presence of hypertension and edema suggests (11)Formal hearing assessment if family acute nephritis. Abdomen should be examined history of hearing loss or hematuria for renal enlargement,tenderness and the persistent for over 6 Months

Annals of ICH, Calcutta 4 3 (12)Check urine of parents/ siblings if persists, then one should rule out UTI and hematuria is persistent continue checking urine and BP every 3 Isolated asymptomatic microscopic hematuria: months. Again, detection of significant proteinuria or hypertension should prompt Incidental finding of isolated microscopic early referral to paediatric nephrologist. If hematuria is relatively common. Repeat microscopic hematuria persists then consider urinalysis should be done without exercise at urine Ca: creatinine ratio and urinalysis of the least 3 times over 3 weeks. If hematuria parents/ siblings. resolves, then routine care continues. If it

References 1. A practical primary care approach to haematuria www.uptodate.com in children. Steven C Diven, L.B. Travis, 4. Oxford Specialist Handbook in Paediatric PaedtrNephrol (2000) 14:65-72 Nephrology, Lesley Rees, Paul A Brogan, Detlef 2. Evaluation of haematuria in children. Kevin E, Bockenhauer, Nicholas J.A. Webb C. Meyers. Urol Clin n Am 31 (2004) 559-573 5. Clinical Paediaric nephrology, 3rd editon, 3. Evaluation of haematuria in children. Nicholas Webb & Robert Postlethwaite. PEDIATRIC NEPHROLOGY DIVISION Institute of Child Health

Well equipped PEDIATRIC NEPHROLOGY DIVISION including PEDIATRIC HEMODIALYSIS facility for the first time in Eastern India, at a very affordable cost, under the care of Pediatric Nephrology team in the state. Facilities available : (i) It is a 6 bedded fully Air Conditioned ward, including one Hemodialysis bed and one Peritoneal dialysis bed.(ii) All modern facilities including Multipara monitors etc (iii) Highly trained staffs round the clock.(iv) Twice weekly Nephrology OPD clinic and daily inpatients visits by nephrologists team. Services Offered: 1. Hemodialysis. 2. Peritoneal dialysis and CAPD initiation. 3. Kidney biopsy 4. Treatment of all types of Kidney problems in children including Nephrotic syndrome, Acute Nephritis. Acute kidney disease, chronic kidney disease, tubular disorders etc.

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4 4 Vol 18 No 1 January – JUNE 2018 Oral Allergy Syndrome Indrani Roy Medical Officer, Allergy Clinic, Institute of Child Health, Kolkata

Introduction i) Food allergens directly penetrate the gastro Oral Allergy Syndrome(OAS)is an IgE intestinal barrier eg.egg, milk, wheat etc. mediated hypersensitivity reaction caused by These are called class I food allergens. cross reacting homologous proteins shared by ii) Food proteins that are homologous to pollens and food proteins1. pollen proteins that penetrates the OAS primarily causes localized oropharyngeal respiratory tract cause secondary symptoms on ingesting fresh plant based sensitization. Primary sensitization is being foods in individuals with pollen caused by pollen proteins . These are class hypersensitivity. But systemic symptoms II food allergens and are typically plant including anaphylaxis have also been recorded. food eg.fresh vegetables ,fruits and nuts. These class II food allergens are Pollen induced allergic rhinitis is often responsible for causing OAS4,5. associated withOAS2. A few words about the homologous proteins OAS normally developes after sensitization to of allergens are needed for better pollens has occured. Therefore symptoms can understanding. develope to foods that were earlier tolerated. The crude allergen extract contains a complex There is a regional variation of OAS mixture of allergenic and non allergenic depending on the difference in pollen components. Clinically significant allergenic exposures and existing local dietary patterns. components have been identified and purified Changes in environmental exposure can also by molecular cloning techniques and adopted lead to sensitization. There is a report of 2 into the World Health Organization / patients who tolerated jackfruit while they International Union of Immunization Society resided in Philippines (a birch free region) but (WHO/IUIS), Nomenclature data base, once developed OAS to jackfruit while they were they have been biochemically and immune - in Switzerland where birch pollen was chemically characterized6. prevalent3. These allergenic molecules are classified into Pathopysiology protein families depending on the structure IgE mediated food allergy sensitization may and function of these proteins. Different occur in the following ways. allergens often share common proteins which

Annals of ICH, Calcutta 4 5 results in immunological cross reactivity. There systemic reactions. Data suggested that LTPs are 9 principal allergen families that manifest may sensitize through the gastro enteral tract cross reactivity due to structural similarity of , as well as through the respiratory tract10. 7 the proteins . Of these, Prolifin, Pathgenesis It has been noted that plant related proteins Related Proteins (PR10),Lipid Transfer (both pollen and plant based food) often Protein(LTP)play significant role in OAS. trigger systemic symptoms as well as localized i) Prolifin: (12-15KDA)present in pollens of symptoms like OAS. Therefore a more trees or weeds and food of plant origin. inclusive and broader term “ Pollen Food Sensitive to heat and digestion.eg: Natural Allergy Syndrome” or (PFAS) has been rubber latex( Hevea brasiliensis) allergen Hev coined.PFAS includes a wide range of b8. symptoms from OAS to Anaphylaxis. Prolifin group of protein is one of the Some of the documented pollen- food trigger factor in latex-fruit cross associations are as follows:8,9 8 reactivity . i) Natural rubber latex( Hevea brasilensis) ii) PR10( pathogenesis related protein) : pollen with Banana, Tomato, Avacado (17kDA), most of them are sensitive to and Potato. heat and digestion. Present in pollens, ii) Ragweed(Ambrosia sp)pollen with pomeceous fruits , stone fruits, vegetables Banana ,Water melon ,Cucumber etc. and nuts . eg Birch pollen allergen Bet v iii) Mugwort(Artemesia vulgaris)pollen with 1, Soya bean Gly m 4, Apple Mal d 1, spices like corriandar (dhania), fennugric Peanut Ara h 8 etc. Primary sensitization (methi) cumin(jeera)dill etc. occurs to inhalation of Bet v1 and secondary sensitization occurs to fruits iv) Birch( Betula venucosa )pollen with ,vegetables and nuts sharing the Apple, Almond ,Peanut ,Soya bean etc. homologous proteins of PR10 family v) An Indian study documents)11 respectively. Clinical features of OAS/PFAS12 iii) Lipid Transfer Proteins (LTP)- ( 7-9kDA) Older children and adolescents are mostly are resistant to heat and digestion. Present affected. in fruits ,vegetables, nuts and pollens. Clinical features of PFAS may be local or LTPs can cause allergies to fruits and vegetables systemic. without having associated pollen allergies9. A) Local : Usually confined to the oropharynx. LTPs in fruits and vegetables (eg grapes, apple, These occur with rapid onset of itching and lettuce,peach, peanut etc.)can cause primary /or tightening of the lips,tongue,palate and sensitization and can cause systemic reactions throat. The itching might spread to the ears. including anaphylaxis . LTPs being resistant to heat and digestion cause higher rates of Angioedema of the lips.

4 6 Vol 18 No 1 January – JUNE 2018 Tightness in the throat due to laryngeal With advancement of technology, oedema. recombinant allergen proteins are used for The symptoms are short lived. detecting specific IgE with good result. B) Systemic symptoms include the following As in case of other food allergy condition, the Double Blind Placebo Controlled Food i) Gastro intestinal- abdominal cramps, Challenge is still the gold standard for vomiting ,diarrhea. detecting OAS/PFAS. ii) Respiratory- Sneezing ,running nose, Management breathing distress and wheezing There is no standard protocol for iii) Skin – Urticaria, angioedema. management. iv) Ocular –Conjunctivitis OAS/PFAS preventive management v) Anaphylaxis. Generally patients are advised to avoid the Diagnosis offending fruit and vegetable specially in the uncooked form. Like in all cases of food related allergy,clinical history is the corner stone of diagnosis of Mild heating/cooking of fruits denatures heat OAS/PFAS. Onset of symptoms , seasonal labile homologous proteins and can be variation of severity of symptoms, specially consumed without any adverse effect. during a particular pollen season are important Certain studies show that LTPs are found in markers. higher concentration in the skin of the apple. Skin Prick Test and specific IgE tests with Therefore while the whole fruit can causes commercial extracts are not very reliable symptoms the flesh of the fruit (discarding predictors for OAS. The reason being as the skin) is well tolerated. follows :- b) Symptomatic management i) Most of the homologous allergen i) Anaphylaxis is treated according to the proteins are sensitive to heat and standard protocol. proteolytic digestion. Hence much of it ii) OAS can be treated with antihistamines. is lost during extraction process. c) Immunotherapy remains a debatable and ii) The proteolytic enzymes present in fruits unproven approach for treatment of PFAS/ and vegetables degrade the allergenic OAS proteins. Conclusion To avoid these draw backs, SPT with fresh Oral Allergy Syndrome or Pollen Food fruits and vegetables have been tried with Allergy Syndrome is a food allergy that occurs better diagnostic utility compared to due to cross reactivity between pollen proteins commercial extracts. Frozen fruits and and protein in plant based food like fresh 13 vegetables are also used with good result . fruits, vegetables and nuts. In most cases

Annals of ICH, Calcutta 4 7 pollens cause the primary sensitization. of diagnosis of OAS/PFAS. SPT and specific Symptoms are mild, short lived and mostly IgE for food allergens are less reliable localized in the oropharyngeal region. But predictors. systemic reactions including Anaphylaxis can Avoidance of offending food items remains occur as well. Clinical history is the corner stone the mainstay of management. References 1) Werfel T, Asero R,Ballmer –Weber BK, Beyer Human Allergic Disease,ed Leung Donald YM, K, Eurique E, Knulst AC, Mari A, Muraro Szefler Stanley J,Bonella Francisco A,Cezini A, A,Ollert M,Poulsen LK, Worm M, Vettis S, Sampson Hugh A. Pediatric Allergy Principles Hoffman-Sommergruber K : Position Paper of and Practice,3rd edition,Elsevier. the EAACI: food allergy due to immunological 8) Ebo DG, Bridts CH,Hagen Dorens, M M,De cross reactivity with common inhalant allergens. Clarke LS, Stevens WJ. The prevalance and Allergy 2015 Sep 70(9): 1079-90 doi 10101111/ diagnostic value of specific IgE antibodies to all.12666 E pub 2015 July 7 accessed on inhalant, animal and plant food and ficus 21.3.2018. allergens in patients with natural rubber latex 2) Dondi A, Tripodi S,Panelta V, Asero R,Businco allergy Acta Clin Belg 58 :183-189 2003. AD, Bianchi A et al: Pollen Induced Allergic 9) Fernandez – Rivas M, van Ree R, Cuevas M : Rhinites in 1360. Italian Children : Allergy to rosaceae fruits without pollenosis. J Comorbodities and determinants of severity. Allergy Clin Immunol,100:728-733,1997. Padiatr Allergy Immunol 24 742-751,2013. 10) Borghesan F, Mistrello G, Ron carolo D,et al: 3) van Ree R : Clinical importance of cross reactivity Respiratory allergy to lipid transfer protein. Int in food allergy. Curr Opin Allergy Clin Immunol Arch Allergy Immunol 147: 161-165,2008. 4: 253-2240,2004. 11) Dhyani A, Arora N, Jain VK, Sridhara S, Singh 4) Nowak-Wegrzyn A, Sampson HA and Sincherer BP: Immunoglobulin E( IgE)- mediated cross SH: Food Allergy and adverse reaction to foods reactivity between Mesquit pollen protein and ed: Kleigman Stanton , St-Greeme, Schor: lima beans: edible legume: Clin Exp Immunol Nelson Text book of Pediatrics Vol I First South 2007 Sep 149(3):517-524. Asia Edition Elsevier. 12) Anhoej C, Backer V, Notle H : Diagnostic 5) Yagami T,Haishima Y, Nakamua A, Osuma H, evaluation of grass and birch allergenic patients Ikejawa Z : digestibility of allergen extracted from with oral allergy syndrome. Allergy 56:584- natural rubber latex and vegetable food s. J 532,2001. Allergy Clin Immunol:106: 752-762;2006 13) Begin P, Des Roches A,Nguyen M,Masse MS et 6) Brietender H, Chapman MD : Allergen al : Freezing does not alter antigenic properties nomenclature . Lucky RF, Ledford DK. Allergen of fresh fruits for skin testing in patients with and Allergen Immunotherapy, 5th birch tree pollen induced oral allergy syndrome. edition,2014,CRC Press BOCA. J Allergy Clin Immunol 127:1624-1626 2011. 7) Hamilton RG: Laboratory Diagnosis of

4 8 Vol 18 No 1 January – JUNE 2018 Recommended Vaccinations for Asplenic and Hyposplenic Children Rina Ghosh Clinical Tutor, Incharge, Immunization Dept., Institute of Child Health, Kolkata The spleen is crucial in regulating immune type b (22%), homeostasis through its ability to link innate Neisseria meningitidis2. and adaptive immunity and in protecting Thus, asplenic patients are at particular risk against infections. The spleen is the largest for infections due to encapsulated organisms. secondary immune organ in the body and is Therefore vaccination with pneumococcal responsible for initiating immune reactions to (both conjugate and polysaccharide), Hib blood-borne antigens where encapsulated conjugate, meningococcal conjugate and bacteria are introduced to B cells and typhoid conjugate vaccines is indicated in production of new antibodies is initiated. addition to all routine vaccines3. Functions of the spleen are carried out by two The term “overwhelming post-splenectomy main compartments of the spleen - white pulp infection” (OPSI) refers to a rapid fatal and red pulp. The red pulp is a blood filter syndrome occurring in individuals following that removes foreign material and damaged removal of the spleen, but is largely and effete erythrocytes. White pulp is interchangeable with “asplenic sepsis.” OPSI composed of lymphocytes, macrophages, can progress from a mild flu-like illness to dendritic cells, plasma cells which are largely fulminant sepsis in a short time period and responsible for initiating immune reactions1. has high mortality rate (up to 50% despite The term “asplenia” refers to the absence of maximal treatment).Estimated incidence of the spleen, a condition that is rarely congenital OPSI is around 0.23–0.42% per year, with a and mostly post-surgical (due to splenic lifetime risk of 5%2. rupture from trauma or for hematological, The risk of infection is higher in subjects immunological, or oncological reasons). The affected by haematological diseases as sickle impairment of splenic function is defined as cell anaemia and thalassemia major or hyposplenism, an acquired disorder caused by lymphoproliferative disorders (e.g. Hodgkin's several diseases (hematological and disease, non-Hodgkin's lymphomas etc.)4,5. immunological disorders, malaria, splenic vein and also in congenitally asplenic children than thrombosis, infiltrative diseases such as those with post traumatic or elective sarcoidosis, amyloidosis, tumors or cysts). splenectomy. Asplenia and hyposplenia are important risk factors for invasive infections in particular with Furthermore, age at time of splenectomy encapsulated bacteria as Streptococcus pneumoniae seems to play an important role in determining (responsible for more than 50% of infections), risk of infection: incidence of OPSI is higher

Annals of ICH, Calcutta 4 9 in patients younger than 16 y (particularly recommended. If this series is not finished younger than 5 y)2,4. The risk is highest during before splenectomy then as many doses, to the first 2 years following splenectomy. get 4 doses, as possible, should be As spleen removes infected erythrocytes - administered (Table 1). asplenic individuals are also at increased II. Haemophilus influenzae type b severity to some parasitic infections such as6. vaccine • Malaria (particularly primary infection) Haemophilus influenzae type b (Hib) • Babesia (Babesiosis is a rare tick-borne conjugate vaccine causes memory infection endemic to certain countries responses by eliciting T cell immunity and (including North and South America, is part of the routine childhood series. All Europe, Asia and Africa) and asplenic children should receive Haemophilus patients travelling to these areas should influenzae type b (Hib) conjugate vaccine take precautions to avoid tick bites (Table 2). • Infection with Capnocytophaga Most individuals are immune even if Canimorsus (after dog or cat bite also unimmunized by 6 years of age. occur at an increased rate in asplenia patients). III. Meningococcal vaccine Splenectomy vaccine protocol for Meningococcal vaccines available for use in pediatric patients7 India are quadrivalent meningococcal Time frame: conjugate vaccines (Menactra - MenACWY- • The ideal time from vaccines to transplant D) and the quadrivalent meningococcal is dependent on the vaccine status of the polysaccharide vaccine (MPSV4). All children candidate but in general all vaccines should should receive Meningococcal conjugate be finished 2 weeks before surgery to vaccine (Table 3). Regular booster doses are allow for appropriate immunity to recommended to asplenic patients in order develop. to maintain a high level of protective • If pre-splenectomy vaccines are not circulating anti-bodies7. possible then the vaccines should be given • The quadrivalent meningococcal >2 weeks postop except when there is conjugate vaccine (Menactra - MCV4) is immunosuppression then vaccines should the preferred choice as it provides be delayed until 3 months post-op which immunological memory and protection is typically when the period of intense for longer duration than polysaccharide immunosuppression is over. vaccine. Menactra should not be given In addition to all routine vaccinations emphasis with the primary series of Pneumococcal should be given for the following vaccinations. conjugate vaccine. I. • The quadrivalent meningococcal In general, all children should receive the polysaccharide vaccine (MPSV4) does not routine 4 doses PCV13 series as induce immunological memory and in

5 0 Vol 18 No 1 January – JUNE 2018 Table 1 : Pneumococcal vaccine

Pneumococcal Conjugate Vaccine Pneumococcal Polysaccharide Vaccine (PCV) # (PPV)* 2nd Booster Age (at diagnosis) Child 1st dose 5 years after Primary Course Booster 3rd Booster** (>2 yrs of age) 1st dose PPV23 6 weeks to 6 3 doses, minimum 1 dose at12- 15 months 1-month apart months of age Primary course 1 dose at 12 -15 complete months of age 7-11 months No previous 2 doses, 1 month 1 dose at 12 –15 doses apart months of age Primary course 1 dose at complete diagnosis 12-23 months No previous 1 dose 1 dose (2 mths doses after last dose) 4 doses complete 1 dose 1 dose 1 dose (at least 2 months post PCV) 2-5 years No previous 1 dose at 2nd dose (2 mths 1 dose 1 dose 1 dose doses diagnosis after the 1st dose) (at least 2 months post PCV) 1 dose 1 dose 1 dose 1 dose >5 years (2 months post PCV)

# PCV can be either PCV10 or PCV13. 13 valent PCV should be the preffered vaccine in case of asplenia/Hyposplenia patients * PPV is the PPV23 (Pneumovax 23) ** The third dose of PPV23 should be given at 65 years of age. Repeated doses of PPV23 might cause hypo immunization; therefore total number of PPV23 should not exceed 3 doses7. Table 2 : Haemophilus Influenzae type b vaccine

Table 3 : Meningococcal vaccine

* Menactra must be administered at least 4 weeks after completion of PCV13 series and never to be used simultaneously with PCV13.

Annals of ICH, Calcutta 5 1 fact repeated vaccinations cause hypo antibiotic supply with instructions to take in immunization and therefore not the event of any sudden onset of unexplained recommended. fever, malaise, chills or other constitutional Conclusions symptoms. Prophylactic antimicrobial therapy All asplenic and hyposplenic patients and their is indicated in selected people. An higher risk families should be educated and given written of OPSI is documented in asplenic subjects information about the risk of OPSI and with haematological malignancies, especially strategies to minimize the threat, besides their in the first 2 year after splenectomy. Therefore, general practitioners should be informed for therapy with oral penicillin in this category of the management of infectious episodes. patients for a period of 2 year is suggested. Vaccinations against S. pneumoniae, N. Malaria prophylaxis for travelers in endemic meningitidis, H. influenzae type b and influenza areas is recommended to avoid severe virus are strongly recommended in addition complications of the disease. Evidence based to other routine vaccinations. Vaccinations prevention data to reduce the risk of infection should be administered at least 2 weeks before in these individuals are accumulating and surgery in elective cases or at least 2 weeks after the surgical intervention in emergency specific hospital protocols should be available cases. Early empirical antimicrobial therapy for to all healthcare workers in order to minimize febrile episodes is indicated for these patients; the risk of infections potentially fatal in those they should have a reserve or standby fragile patients2.

References 1. Dijkstra, CD, Veerman, AJPJones, TC, Ward, 54 (2001), pp. 214-218 JM, Mohr, U, Hunt, RDNormal Anatomy, 5. M.L. BrigdenOverwhelming postsplenectomy Histology, Ultrastructure, RatMonographs on infection still a problem West J. Med., 157 (1992), Pathology of Laboratory Animals: Hemopoietic pp. 440-443. System1990BerlinSpringer-Verlag18593 6. C.J. Sawmiller, S.J. Dudrick, M. 2. Hum Vaccin Immunother. 2017 Feb; 13(2): 359– HamziPostsplenectomy Capnocytophaga 368.Published online 2016 Dec 8. canimorsus sepsis presenting as an acute 3. Guidebook on Immunization 2013–14, abdomen Arch. Surg., 133 (1998), pp. 1362-1365 Edition : 2014, Publishers: Indian Academy of 7. https://www.cdc.gov/vaccines/schedules/ Pediatrics, National Publication House, Gwalior, downloads/child/0-18yrs-child-combined- ch : Immunization in Special Situations, pg 373 schedule.pdf, Recommended Immunization 4. D.J. WaghornOverwhelming infection in asplenic Schedule for Children and Adolescents Aged 18 patients: current best practice preventive Years or Younger, UNITED STATES, 2018, measures are not being followed J. Clin. Pathol., accessed on 17.07.2018

5 2 Vol 18 No 1 January – JUNE 2018 Atopic Dermatitis – General Skin Care Practices Raghubir Banerjee Consultant, Dept of Dermatology, Institute of Child Health, Kolkata

Atopic dermatitis is exacerbated by numerous and surfactant-based cleansers and better be triggers and hence the care of the skin in avoided, as they often increase skin dryness, children is of primary importance to ensure and cause irritant and allergic contact dermatitis disease control and the parents or caregivers in atopic children6-8. Syndets or non-soap should be adequately instructed and tutored cleansers with a pH of 5.5 and are the soaps for this. They should know about bathing of choice in these patients . They maintain the practices and use of emollients as this is pivotal acid mantle and are less irritant in children . in maintaining the skin barrier in atopic subjects. Cleansing agents with added antiseptics and Proper cleansing practices hydrate the skin and perfumes are not to be used as they may help remove crusts, irritants like sweat, potentiate skin damage and may cause irritant allergens and mechanically remove bacterial reaction . contaminants in case of bacterial The use of bleach baths have been found to superinfection of the skin in atopic eczema. reduce staphylococcal colonization and The total or maximum duration of bath decrease AD severity9-12. The process involves should not exceed 5-10 minutes at the most soaking the body from neck downwards in as it is seen that prolonged exposure can harm a tub filled with water (about 150 litres) in the structural integrity of the skin and damage which half a cup of 6% household bleach the barrier as a whole1. The temperature of has been mixed .As a result of space crunch , the bath or the water should be near body parents find it hard to give bleach tub baths temperature that is lukewarm or cool, as to their children. In such conditions 1 temperature extremes can result in flare and teaspoonful (around 5 ml) of bleach can be increase in the itching sensation2. The frequency added to a bucket of around 15 litres of of bathing recommended is at least once a water and subsequently a soft cloth soaked day which may vary in summer months3. into this solution can be utilised for soaking The bath is usually followed by application on the skin for around 10 to 15 minutes in of emollient right after the bath after patting general. the skin dry to maintain skin hydration and The use of baby shampoos is widely practised prevent dryness4. Vigorous rubbing and in our country. They may aggravate dryness scrubbing during bath is not advised as it leads in the cold season . Proper care needs to be to barrier damage and may aggravate the itch5. taken to wash off residues of these cleansing Normal bath soaps are usually alkaline soaps agents from the body folds2 like the hairline,

Annals of ICH, Calcutta 5 3 retro auricular region, etc13. use of smooth, soft, loose, full-sleeved cotton Water hardness also plays a significant role . clothes in patients with AD will help to reduce The scum produced due to exposure to hard skin irritation and pruritus . water has been thought to be an aggravating The environment also plays a role in these factor in children with AD . A cohort study patients as low humidity and low temperature of 1638 Spanish cohorts did not find any may cause a decrease in skin barrier function association between eczema and water and susceptibility to mechanical stress17. Heat hardness at home or bathing exposure during , humidity and sweating can worsen AD2. In 14 the first 4 years of life . A more recent study hot weather, using air conditioning or use of of 1303 three month old infants concluded desert coolers during summer can be very that high domestic Calcium carbonate levels helpful. For dry climates, humidifiers have been 15 were associated with an increased risk of AD . used for AD patients, but no systematic studies In another randomized controlled trial of 336 have been done. In patients who cannot afford children with moderate to severe AD, the use air conditioning, one can recommend bathing of ion-exchange water softeners did not twice a day and being under the fan and well- significantly improve the Six Area Six Sign ventilated areas. Atopic Dermatitis (SASSAD) score16. Some patients with AD develop dry skin or The choice of clothes for the child is important also . The coarse irritating fabrics may increased cutaneous inflammation with precipitate primary skin irritation and are frequent swimming in public pools. The usually avoided in such conditions . The use amount of free residual chlorine may impact of occlusive clothing that can cause heat the skin barrier and contribute to AD sensation and better be avoided. Hence the exacerbation18.

References dermatitis with topical therapies. J Am Acad 1. Bouwstra JA, de Graaf A, Gooris GS, Nijsse J, Dermatol 2014; 71: 116-132. Wiechers JW, van Aelst AC. Water distribution and related morphology in human skin at 4. Simpson E, Trookman NS, Rizer RL, Preston different hydration levels. J Invest Dermatol N, Colon LE, Johnson LA, et al. Safety and 2003; 120: 750-758. tolerability of a body wash and moisturizer when applied to infants and toddlers with a 2. Langan SM, Bourke JF, Silcocks P, Williams HC. history of atopic dermatitis: results from an An exploratory prospective observational study open-label study. Pediatr Dermatol 2012; 29: 590- of environmental factors exacerbating atopic 597. eczema in children. Br J Dermatol 2006; 154: 979-980. 5. Kim JE, Kim HJ, Lew B, Lee KH, Hong SP, Jang YH, et al. Consensus guidelines for the 3. Eichenfield LF, Tom WL, Berger TL, Krol A, treatment of atopic dermatitis in Korea (Part I): Paller AS, Schwarzenberger K, et al. Guidelines General management and topical treatment. Ann of care for the management of atopic dermatitis; Dermatol 2015; 27: 563-577. section 2. Management and treatment of atopic

5 4 Vol 18 No 1 January – JUNE 2018 6. Shukuwa T, Kligman A M. Disaggregation of 3. Katayama I, Kohno Y, Akiyama K, Aihara M, corneocytes from surfactant-treated sheets of Kondo N, Saeki H, et al. Japanese Guidelines stratum corneum in hyperkeratosis on psoriasis, for Atopic Dermatitis 2014. Allergology ichthyosis vulgaris and atopic dermatitis. J International 2014; 63: 377-798. Dermatol 1997; 24: 361-369. 4. Font-Ribera L, Gracia-Lavedan E, Espluques A, 7. Shaughnessy CN, Malajian D, Belsito DV. Ballester F, Jimenez-Zabala A, Santa Marina L, Cutaneous delayed hypersensitivity in patients et al. Water hardness and eczema at 1 and 4 y of with atopic dermatitis: reactivity to surfactants. J age in the INMA birth cohort. Environ Res 2015; Am Acad Dermatol 2014;70:704-708. 142: 579-585. 8. Sidbury R, Tom WL, Bergman JN, Cooper KD, 5. Perkin MR, Craven J, Logan K, et al. Association Silverman RA, Berger TG, et al. Guidelines of between domestic water hardness, chlorine, and care for the management of atopic dermatitis: atopic dermatitis risk in early life: A population- Section 4. Prevention of disease flares and use based cross-sectional study. J Allergy Clin. of adjunctive therapies and approaches. J Am Immunol 2016; 138: 509-516. Acad Dermatol 2014;s71: 1218-1233. 6. Thomas KS, Koller K, Dean T, O’Leary CJ, Sach 9. Huang JT, Abrams M, Tlougan B, Rademaker TH, Frost A, et al. A multicentre randomised A, Paller AS. Treatment of staphylococcus controlled trial and economic evaluation of ion- aureus colonization in atopic dermatitis decreases exchange water softeners for the treatment of disease severity. Pediatrics 2009; 123: 808-814. eczema in children: the Softened Water Eczema 0. Huang JT, Rademaker A, Paller AS. Dilute bleach Trial (SWET). Health Technol Assess 2011; 15: baths for Staphylococcus aureus colonization in 1-156. atopic dermatitis to decrease disease severity. Arch 7. Engebretsen KA, Johansen JD, Kezic S, Dermatol 2011; 147: 246-247. Linneberg A, Thyssen JP. The effect of 1. Barnes TM, Greive KA. Use of bleach baths for environmental humidity and temperature on the treatment of infected eczema. Australas J skin barrier and dermatitis. J Eur Acad Dermatol Dermatol 2013; 54: 251-258. Venereol 2016; 30: 223-249. 2. Wong SM, Ng TG, Baba R. Efficacy and safety 8. Seki T, Morimatsu S, Nagahori H, Morohashi of sodium hypochlorite (bleach) baths in M. Free residual chlorine in bathing water reduces patients with moderate to severe atopic the water-holding capacity of the stratum dermatitis in Malaysia. J Dermatol 2013; 40: 874- corneum in atopic skin. J Dermatol 2003; 30: 480. 196-202.

Neurodevelopmental Clinic

Neurodevelopment clinic is held every Friday at 12 noon. All types of developmental delay, cerebral palsy, speech delay, poor scholastic performance, autism, ADHD are dealt in this clinic.

Annals of ICH, Calcutta 5 5 Highlights of PCR Based Detection of Genetic Disorders and Pathogens Pranab Roy Senior Consultant, Molecular Biology, Dept. of Lab Medicine, Institute of Child Health, Kolkata Polymerase Chain Reaction was discovered desired temperatures for the chosen times. by Dr Kary Mullis1 accidentally when he was Such PCR machines have been available for driving along a highway in California one starry the last three decades. The products of the night in 1984. Deeply pondering about the PCR are visualized by gel electrophoresis in mechanism of DNA replication, he hit upon agarose and staining the DNA bands with the idea that repeated cycles of DNA synthesis fluorescent dyes. Originally, Ethidium by DNA Polymerase using primers specific Bromide was used which intercalates between for a particular gene would amplify the DNA the two strands of DNA and fluoresces in sequence of the template exponentially. At that UV light. Since the mutagenic effects of EtBr time, only E.coli DNA Pol I was and UV radiation are known, a safer commercially available. Since the first step of alternative is found in Sybr Green dye which the cycle is heating at 950C, E.coli polymerase fluoresces when bound to DNA with blue gets inactivated and one had to add the enzyme light3. We are using the latter method of for each cycle 30 times. Theoretically, one detection. should get amplification of the target sequence A novel modification of the method came 30 to 2 folds which means that the amount of around the turn of the century. Reverse template DNA from a single cell, which is Transcription of mRNA to produce cDNA roughly 1 pg would be amplified to 1 mg (Complementary DNA) followed by PCR amplicon after 30 cycles of PCR. This amount amplification of the particular gene reveals its of DNA is enough for molecular cloning or expression into RNA, which is the precursor direct sequencing. Dr Mullis was awarded the of the gene product, protein. Thus the level Nobel prize for his discovery. of gene expression could be quantified using Later the process was automated using RT-PCR4. But the same acronym is also used thermostable Taq DNA Polymerase from the for another technique which is mostly used bacteria Thermus aqaticus obtaind from hot nowadays for detection of genetic disorders spring2. This enzyme is quite stable at 950C or infection by pathogens. This is Real Time and one need not add it after each cycle. So PCR or qPCR (Quantitative PCR) which one can program the DNA Thermocycler for involves detection of the amplicons in situ, the three steps of melting the template DNA, within the reaction tube. So there is no need annealing of the short primer of post-PCR gel electrophoresis. The oligonucleotides, and polymerization at the detection here depends on the fluorescence

5 6 Vol 18 No 1 January – JUNE 2018 of the fluorophore which is either tagged with pathogens involved is numerous. Changes in dNTPs or the hybridization probe added for the population as it ages and the increased a particular gene to be amplified. Two number of patients with immuno- methods are used for such fluorescence compromised conditions have increased the detection, one is High Resolution Melt Analysis number of individuals at risk. Pathofinder (HRMA) where the melting temperatures of B.V.is a company at Maastricht, the different gene specific probes tagged with Netherlands specializing in manufacturing different fluorophores are analysed different kits using multiplex RT-PCR, which automatically by the software available with we are attempting to use. the instrument. The second is called TaqMan The RealAccurate® Quadruplex Respiratory 5 Chemistry where gene specific probe PCR Kits are six separate multiplex PCR Kits sequences are tagged with a fluorophore at which can detect and differentiate 22 5’-end and a quencher molecule at the 3’-end. respiratory pathogens in total. The This probe does not exhibit fluorescence, Quadruplex assays are one-step reverse being quenched by the quencher. As PCR transcriptase PCR assays which are designed progresses, the Taq Polymerase which has 5’- for fast detection on real-time PCR instruments exonuclease activity, encounters the probe using 4 different detection channels (FAM, hybridized with the amplicon. This releases MAX, Texas Red and TYE665). the fluorophore, which exhibits fluorescence This saves valuable time in diagnosing the and detected at the particular wavelength in a pathogen in case of gastro- enteric, respiratory, channel. The modern thermocyclers have meningo or derma infections, so that the multiple channels which can detect different proper antibiotic could be administered. This fluorophores which are released from would prevent over-use of antibiotics in different amplicons produced by multiplex infectious diseases and reduce the PCR. In this technique, several sets of primers, development of multidrug resistant micro- specific for different genes which may be organisms. specified for different microbes are amplified together and detected by gene specific In genetic diseases where the causative genes hybridization probes. Different channels have been identified and point mutation or would capture the fluorescence released by insertion/deletions been mapped which lead different fluorophores. to different diseases, RT-PCR has been extensively used. Examples are beta Advances in technology and engineering of thalassemia, cystic fibrosis and ankylosing RT-PCR (qPCR) have yielded kits which can spondylitis. The causative genes are beta identify a pathogenic bacterium or virus from globin, CFTR (Cystic Fibrosis Trans- a panel of 22 possible candidates all at the membrane Regulator) gene and HLA-B27 same time. Acute respiratory tract infection is gene respectively. Various mutations in each the most widespread type of acute infection of these genes have been mapped precisely in adults and children. The number of in different laboratories and reported5,6,7.

Annals of ICH, Calcutta 5 7 Using primers specific for the wild type or In future, these techniques would be adopted the mutant sequences of the gene, one can by most advanced clinical diagnostic labs, obtain positive or negative signals with though cost is a factor to reckon with. But Taqman chemistry. ARMS or Amplification the accuracy and speed of detection would Refractory Mutation Screening is another method for the detection of specific point overcome the cost factor which may come mutation in the target gene. down in times to come.

References 1. Saiki, R., Gelfand, D., Stoffel, S.,Scharf, S., quenched probe system useful for detecting PCR Higuchi, R., Horn, G., Mullis, K., Ehrlich, Product and Nucleic Acid Hybridization, H.(1988) Primer directed enzymatic amplification Genome Research, Cold Spring Harbor of DNA with a thermostable DNA Polymerase, Laboratory Press, 4: 357-362. Science, 239, (4839), 487-491. 5. Galanello, Renzo; Origa, Raffaella (2010). "Beta- 2. Arezi, B., Zing, W., Sorge, J.A., and Hogrefe, thalassemia". Orphanet Journal of Rare H.H.(2003) Amplification Efficiency of Diseases. 5 (1): 11. doi:10.1186/1750-1172-5- Thermostable DNA Polymerases. Analytical 11 Biochemistry, 321, 226-235. 6. McIntosh I, Cutting GR (1992). "Cystic fibrosis 3. Ponchel, F.et.al.(2003) Real Time PCR based on transmembrane conductance regulator and the SYBR Green 1 Fluorescence: An alternative to etiology and pathogenesis of cystic fibrosis". the TaqMan assay for a relative quantification of FASEB J. 6 (10): 2775–82 gene rearrangements, gene amplifications and 7. Sampaio-Barros PD, Bortoluzzo AB, Conde gene deletions, BMC Biotechnology, 3, 18-28. RA, Costallat LT, Samara AM, Bértolo MB (June 4. Livak,K.J., Flood, S.J.A., Marmaro, J., Glusti, 2010). "Undifferentiated spondyloarthritis: a W. and Deetz,K.(1995) Oligonucleotides with longterm followup". The Journal of fluorescent dyes at opposite ends provide a Rheumatology. The Journal of Rheumatology. 37 (6): 1195–1199.

Allergy Department Institute of Child Health, Calcutta

This unit has been serving the field of investigation, therapy and research in allergy for the past twenty five years. Comprehensive management of allergic disorders including detection of offending allergens, immunotherapy and computerised spirometry are done. This unit is recognised by the Directorate of Drugs Control, Govt. of WB as well as the Central Directorate of General Health Service (Drug Section) Govt. of India.

Monday to Friday: 9.30 am to 3 pm, Saturday : 9.30-12.30

5 8 Vol 18 No 1 January – JUNE 2018 Diagnosis of Cystic Fibrosis: What’s New? Surupa Basu Head, Dept of Biochemistry, Institute of Child Health, Kolkata

Cystic fibrosis (CF) is a multisystem autosomal family history and/or a positive newborn recessive disorder caused by mutations in the screening. Sweat chloride <30 mmol/L CF transmembrane conductance regulator is normal threshold for all ages. This has (CFTR) gene. CF, once thought to be a been revised from the threshold of <40 European disease, is not uncommon in the mmol/L in the 2008 guidelines. Indian population. The clinical eye being Exceptions may occur and in such cases trained to identify the presence of symptoms where symptoms strongly support CF along with clinician’s access to specific tests and not an alternative diagnosis, it is have led to an upsurge in diagnosis of CF in recommended to perform CFTR gene Indian children. mutation analysis. CF continues to throw up diagnostic 3. Sweat chloride testing should be challenges due to the varying clinical performed according to approved presentation of the disease, presence of more procedural guidelines published in than 2000 genetic mutations causing variable established, international protocols (e.g. levels of CFTR dysfunction and consequent CLSI 2009 Guidelines). Currently there lack of genotype-phenotype correlation. With are two established methods of sweat significant growth of phenotypic and chloride estimation: the classic ST genotypic information on CF, the 2008 CF developed by Gibson and Cooke by the Foundation diagnosis guidelines have been quantitative pilocarpine iontophoresis test updated in 2015. These have been published and the sweat conductivity test by the in February 2017 issue of The Journal of macroduct sweat collection system and Pediatrics. The CF foundation has laid 27 analysis of electrolytes based on consensus recommendations for diagnosis of conductivity. A diagnosis of CF can be CF. The following discussion enlists the salient made if the sweat chloride value = 60 points; and a summary of revisions compared mmol/L. A second confirmatory ST to 2008 guidelines. following an initial positive result is not 1. CF is diagnosed when an individual has necessary; this is change from the previous both a clinical presentation of the disease guidelines. However, CFTR genetic testing and evidence of CFTR dysfunction. should be performed in all cases 2. Sweat chloride test (ST) continues to diagnosed with CF. For newborns with a remain the gold standard for diagnosis. positive screen and clinical signs and It should be performed on everyone with symptoms of CF or meconium ileus, it signs and/or symptoms of CF, having is recommended to have ST performed

Annals of ICH, Calcutta 5 9 bilaterally and when the infant weighs >2 more are unlikely to have CF. kg and is at least 36 weeks’ corrected 6. Inconclusive diagnosis: for the screened gestational age. The ST should be newborn with a high level of performed after 10 days and within 4 immunoreactive trypsinogen (IRT) weeks of age. following NBS and inconclusive CFTR 4. Suspected cases with borderline sweat functional and genetic testing may be chloride (30-59 mmol/L) on two separate labeled either as CRMS (CFTR related occasions may have CF. in such cases, they metabolic syndrome) or equivalent should be considered for extended genetic CFSPID (CF screen positive, inconclusive analysis and/or CFTR physiologic testing diagnosis). CRMS/CFSPID newborn has such as nasal potential difference (NPD) ST <30 mmo/L and 2 CFTR mutations test in a validated test center. at least 1 of which has unclear phenotypic 5. The latest classification in the Clinical and consequences OR an intermediate ST Functional Translation of CFTR (CFTR2) value with 1 or 0 CF causing mutations. project (www.cftr2.org) should be used For the nonscreened individual with an to aid with CF diagnosis: (1) CF-causing inconclusive diagnosis, they are referred mutation: individuals with 2 copies on to as CFTR - related disorder. It has been separate alleles will likely have CF (clinical defined as a monosymptomatic clinical sweat confirmation is needed, a ST =30 entity (pancreatitis/bronchiectasis/ mmol/L is confirmatory for patients congenital absence of vas deferens) with such genotype). The absence of 2 associated with CFTR dysfunction that CF causing CFTR mutations does not does not fulfill the diagnostic criteria of exclude a diagnosis of CF (2) mutations CF. The terms classic/non-classic CF, of varying clinical consequence (MVCC): typical/atypical CF, and delayed CF A mutation in combination with another should be avoided. CF-causing mutation or with another The tests of CFTR function need not follow MVCC may result in CF. (3) any order, but hierarchically, sweat chloride Uncharacterized/mutation of unknown should be considered first followed by CFTR clinical consequence: mutation that has not genetic analysis, especially in the Indian been evaluated by CFTR2 and may be population where prevalent mutations have disease causing or of variable clinical not been classified in a common mutation test consequence or benign. (4)non-CF panel and due to the presence of many novel causing mutation: individuals with 1 or mutations across the population.

Detailed Reading: of Cystic Fibrosis in Nonscreened Populations. 1. Farrell PM, et al. Diagnosis of cystic fibrosis: The Journal of Pediatrics. 2017; 181, Consensus guidelines from the Cystic Fibrosis Supplement:S52-S57.e2. Foundation.2017. J Pediatr 181, 3. Wiencek JR, Lo SF. Advances in the diagnosis Supplement:S4–S15, 15.e1 and management of cystic fibrosis in the ge- 2. Sosnay PR, White TB, Farrell PM, Ren CL, nomic era. Clin Chem. 2018. DOI:10.1373/ Derichs N, Howenstine MS, et al. Diagnosis clinchem.2017.274670

6 0 Vol 18 No 1 January – JUNE 2018 An Atypical Case of Enteric Fever

*Subrata Chakraborty, **Parthapratim Halder, ***Soham Mitra, ***Samiran Das, ***Tanmoy Khan *Professor, **Assistant Professor, ***Postgraduate, Dept of Paediatric Gastroenterology , Institute of Child Health, Kolkata

Abstract A 5 year old female child presented with pain abdomen, fever and rash progressively involving the lower extremities, buttocks and abdomen. The rash was palpable, purpuric. A primary clinical impression of HSP was made. However skin biopsy ruled out HSP. Blood culture reports were positive for Salmonella typhi. The child was managed as a case of enteric fever leading to resolution of symptoms. Key words : Palpable purpuric rash, progressive, lower extremities, buttocks, abdomen, pain abdomen, HSP, skin biopsy, Widal, blood culture, Salmonella typhi, enteric fever.

Introduction progressive involvement of buttocks, Enteric fever, a severe systemic infection abdomen and mild involvement of the upper caused by Salmonella enterica serovar Typhi(S. extremities. On abdominal examination there typhi) and Salmonella enterica serovar was generalized mild tenderness without any Paratyphi (S. Paratyphi), is a common cause significant organomegaly. The child was of morbidity in the developing countries hemodynamically stable. including India1. The majority of disease A primary impression of Henoch-Schonlein burden is contributed by children and Purpura(HSP) was made. Routine blood adolescents1. investigations were unremarkable except for Summary of Case raised serum CRP. Serum LDH was within normal range. No significant derangement of A five year old female child from Howrah liver function test (LFT) was seen. An presented with pain abdomen,fever(high ultrasonography (USG) of abdomen ruled grade) and rash in the lower extremities since out any organic cause of pain four day duration along with pain in the both abdomen.Biopsy of the skin lesions revealed legs and calf region of similar duration. There leucocytoclastic vasculitis. However was also history of blood in stool during the immunohistochemistry reports of the same time of admission. ruled out HSP. Due to persistent abdominal Rash was erythematous, palpable, purpuric pain, MRI abdomen was done which revealed seen mainly over the lower extremities with terminal ileitis with oedema around ileal region.

Annals of ICH, Calcutta 6 1 Urine culture was sterile. Widal test was clinical presentations of typhoid fever negative. However, blood culture yielded overlapping with that of HSP.3It has been growth of Salmonella typhi. Hence the child hypothesized that the HSP–salmonella was diagnosed as a case of enteric fever. association could have been due to an overall The child was managed with antibiotics (IV anomalous regulation of the lymphoid system Ceftriaxone followed by oral cefixime,oral of the mucosa, possibly modulated by a 4 azithromycin ) and other supportive genetic predisposition . medications. There was significant clinical Complications of enteric fever such as improvement with disappearance of rash and intestinal hemorrhage and perforation are seen abdominal pain at the time of discharge. in <1% and 0.5-1% respectively2. The child was followed up 2 weeks after The mainstay of diagnosis is a positive culture discharge during which there was no onset from blood or another anatomic site. Blood of any new symptoms and the child was culture results are positive in 40-60% of doing well and pursuing regular activities. patients2. Discussion The treatment of uncomplicated enteric fever The common clinical features of enteric fever is Cefixime (20mg/kg/day) for 10- 14 days are high grade fever (95%), coated tongue as the 1st line drug. The 2nd line drugs are (76%), diarrhea (36%), toxicity (29%), Azithromycin (20mg/kg/day) for 7- 10 days, abdominal pain (21%), splenomegaly (17%) Chloramphenicol (50-75 g/kg/day) for 14- etc2. 21 days, TMP-SMX (TMP 8mg/kg/day) for In around 25% cases, a macular or 14 days and Amoxicillin (75-100 mg/kg/day) maculopapular rash (rose spots) may be visible for 14 days1. around 7th to 10th day of illness and lesions In complicated enteric fever, the 1st line drug appear in crops of 10-15 on lower chest and of choice is Ceftriaxone/Cefotaxime (80 – abdomen in last 2-3 days.2In this case, there 100 mg/kg/day) for 10-14days.The 2nd line was erythematous, palpable, purpuric rash drugs are Chloramphenicol (100 mg/kg/day) progressively involving the lower extremities, for 14- 21 days, TMP-SMX(similar dose and buttocks, abdomen and mild involvement of duration as above), Amoxicillin (similar dose upper extremities. and duration as above) and Aztreonam (50- Very few studies in the world have reported 100 mg/kg/day) for 14 days1.

References 1. Kumar P, Kumar R. Enteric fever. Indian J nephritis and Salmonella typhisepticaemia. Pediatr.2017;84(3):227-30. NephrolDiaTransplan. 2001;16(5):1081-82. 2. Kliegman RM, Stanton BF, St Geme JW, Schor Available at https://doi.org/10.1093/ndt/ NF. Nelson Textbook of Pediatrics. 20th 16.5.1081 ed,2016. Vol 2;198.2:1388-92. 4. Zucchini A, Manfredi R. Schonlein-Henoch 3. Youmbissi TJ, Malik TQ, Kumar SA, Rafi A, Al syndrome and Salmonella infection: a new Khursanny AI, Karkar A. HenochSchonlein association? Minerva Pediatr.1992;44:559-63.

6 2 Vol 18 No 1 January – JUNE 2018 A Newborn with Vein of Galen Malformation *Mallar Mukherjee, **Deepa, **Tania Khan *Assistant Professor, **Postgraduate, Institute of Child Health, Kolkata

Abstract A vein of Galen malformation(VGM) is a rare vascular malformation, often resulting in high morbidity or mortality. In the newborn, cardiac failure is the most common presenting, sign and the outcome is particularly poor. As the technique of neurointervention develops, embolizaton is known to be the choice of treatment reducing the mortality rate tremendously. The authors report a case of VGM, diagnosed in uterus. Key Words: Vein of Galen malformation; Cardiac failure; Neurointervention

Introduction output-failure), pulmonary hypertension, Vein of Galen aneurysmal malformation respiratory distress syndrome, and pulmonary (VGAM) was first described by Steinhel in oedema up to multiorgan failure. In infancy 18951. It is a rare congenital, cerebral, (mural type of the VGAM—less, but bigger arteriovenous abnormality with an incidence shunts as direct arteriovenous fistulas within of 1 : 25000. The VGAM develops during the wall of the median prosencephalic vein the 6th to 11th weeks of gestation and can of Markowski), hydrocephalus, macrocrania, already be diagnosed prenatal by ultrasound2. and developmental retardation are relevant. But most often the VGAM is detected in the Rarely seen in VGAM are epileptic seizures, postnatal period3. Multiple shunts with brain showing the damage of the brain. In different arteries are the cause of the aneurysmatic areas of the world, the clinical presentation enlargement of the big unpaired cerebral vein, can differ from the general descriptions in the 4 also called as Vena Galeni. Depending on the literature . Left untreated, the mortality of age of the patient and on the anatomy and newborns with severe cardiac insufficiency 5 angioarchitecture of the malformation, there amounts to 100%, in infancy 72% . The safest are different symptoms. In the neonate targeted treatment of a VGAM and also (choroidal type of the VGAM— multiple therapy of choice is the endovascular arteriovenous shunts because of a contribution embolization—primarily transarterial using a 6-8 of all choroidal arteries before emptying into special kind of glue . Higher rates of a venous pouch), evidence of volume complications and mortality are described for overloading is often dominating: raised other therapeutical methods (transvenous 9 cardiac output per minute, tachycardia, embolization, surgical treatment) . Time and cardiomegaly and cardiac insufficiency (high- method of endovascular embolization

Annals of ICH, Calcutta 6 3 depends on clinical of structure showed extensive colour filling the patient3,10. The Bicˆetre-score is helpful to with turbulent flow.The vessels around evaluate the therapeutical management of it appeared dilated and tortuous. neonates with VGAM. It is based on the There was no significant family history of experience of the research group of congenital anomalies or social history for toxic Lasjaunias with over 300 patients with environment or occupational exposures. VGAM6. Using the scoring system, the Antenatal course was uneventful. Baby was cardiac, cerebral, respiratory, hepatic, and born uneventfully and cried immediately after nephrological state of the patient can be birth and after performing routine steps of assessed. If cardiovascular and neurologic resuscitation,baby was kept at NICU for symptoms are stable (Bicˆetre-score > 12), it observation. On Day 2 of birth,an is recommended to postpone treatment up echocardiography was done,that revealed to the age of 5 to 6 month6,11,12. With a unregressed neonatal pulmonary hypertension. Bicˆetre-score of 8–12 points, an emergency Further postnatal period was uneventful and endovascular embolization should be done. baby remained hemodynamically stable. In case of profound neurological defects or medically uncontrollable cardiac insufficiency MRI brain was done at the age of day4 (Bicˆetre-score < 8), there is no indication for that revealed a Large vein of Galen an invasive procedure6. In former days, the malformation.(Fig. 1, 2, 3) introduction of embolization had a bad Physical examination revealed a weight of outcome (high mortality and morbidity) both 2465g,length 47cm,head circumference in neurosurgical and in conservative treated patients13,14. Recent works of different research groups demonstrated higher survival rates, normal growth and at most mild neurological deficits in VGAM-patients who got a timely, therapeutic embolization6,11,15,16. Case report A 5 days of age term , average gestational age male baby was admitted in NICU.This is the baby of a primigravida,who had hypothyroidism and was on .She had a history of gestational hypertension at third trimester.Early antenatal period was uneventful.However mother underwent antenatal ultrasonography for three consecutive days just prior to delivery because of sudden finding of A well defined cystic SOL measuring 20.8 *20.2cm in the midline along the calyx and posterior to the thalamus.The Fig.1- T1 image showing large VGM

6 4 Vol 18 No 1 January – JUNE 2018 Fig.3- T2 image showing large VGM management of a neonate with VGAM. If cardiovascular and neurologic symptoms are manageable conservatively, the intervention should be done in the age of 5 to 6 months after birth6,10. It has been shown that most of the children who were treated by endovascular embolization showed a normal especially neurological development6. Rodesch et al. Fig.2- T1 image showing large VGM present about 16 neonates with VGAM and 33cm.No visible anomalies were noted at cardiac insufficiency, of which 12 survived birth. Baby developed feeding normally, was effectively after therapy with diuretic hemodynamically stable. Baby was shifted to medication and embolization and such have higher centre for further management. shown a normal neurological development. The 4 untreated ones died shortly after birth Conclusion because of multiorgan failure [18]. Lasjaunias The VGAM can be detected already in the demonstrated with a cohort of 216 patients prenatal period10,17. So the diagnosis of an over a period of 21 years, that 74% of the arteriovenous malformation demands an patients with VGAM treated with intensive interdisciplinary collaboration of endovascular embolization had a normal obstetricians, pediatricians, neuroradiologists, neurological development, about 15% were and neurosurgeons. If there are already moderately retarded and only about 10% of prenatal cardiac insufficiency or/and cerebral the surviving patients show neurological damages, the prognosis for the patient is deficits with a severe disability. 23 children poor10. The time and method of therapeutical died6. In another study of Jones et al. over intervention, respectively, and the endovascular the period of the years from 1987 to 2001, 7 embolization depend on clinical signs and of 13 patients (2 of 8 patients presented as symptoms of the patient [6, 18]. The Bicˆetre- neonates with heart failure and the other 5 score is useful for evaluating the therapeutical patients presented outside neonatal period)

Annals of ICH, Calcutta 6 5 achieved a normal or near-normal outcome screening in an asymptomatic newborn. The after endovascular embolization19. According timing of first embolization with 6 months to the report by Fullerton et al., 14 of 23 of this asymptomatic infant was chosen children who had undergone endovascular according to an evidence-based score. The treatment of the VGAM between the years arteriovenous shunt could be closed before 1983 and 2002 developed well neurologically20. onset of symptoms and without Also Ellis et al. recently reported excellent complications.Patients with VGAM long-term cognitive and functional outcomes presenting symptoms during the neonatal after endovascular occlusions of VGAM21. Most patients with VGAM have neurological period have a worse prognosis regarding the 10,19 symptoms at the time of diagnosis making success of endovascular embolization . the need for treatment obvious. In our case However, clinical signs and symptoms are the diagnosis was a result of ultrasonographic diverse and may differ individually4. References 1. W. E. Dandy, “Experimental hydrocephalus,” “Endovascular management of vein of Galen Annals Surgery, vol. 70, no. 2, pp. 129–142, 1919. aneurysmal malformations. Influence of the 2. C. A. Raybaud, C. M. Strother, and J. K. Hald, normal venous drainage on the choice of a “Aneurysms of the vein of Galen: embryonic treatment strategy,” Child’s Nervous System, considerations and anatomical features relating vol. 26, no. 10, pp. 1367–1379, 2010. to the pathogenesis of the malformation,” 8. V. V. Halbach, C. F. Dowd, R. T. Higashida, P. A. Neuroradiology, vol. 31, no. 2, pp. 109–128, 1989. Balousek, S. F. Ciricillo, and M. S. B. Edwards, 3. G. R. Cumming, “Circulation in neonates with “Endovascular treatment of mural-type vein of intracranial arteriovenous fistula and cardiac Galen malformations,” Journal of failure,” American Journal of Cardiology, vol. Neurosurgery, vol. 89, no. 1, pp. 74–80, 1998. 45, no. 5, pp. 1019–1024, 1980. 9. P. Lasjaunias, R. Garcia-Monaco, G. Rodesch et 4. A. K. Gupta, V. R. K. Rao, D. R. Varma et al., al., “Vein of Galen malformation. Endovascular “Evaluation, management, and long-term management of 43 cases,” Child’s Nervous follow up of vein of Galen malformations,” System, vol. 7, no. 7, pp. 360–367, 1991. Journal of Neurosurgery, vol. 105, no. 1, pp. 10. G. Beucher, C. Fossey, F. Belloy, B. Richter, M. 26– 33, 2006. Herlicoviez, and M. Dreyfus, “Antenatal 5. D. Khullar, A. M. I. Andeejani, and K. R. Bulsara, diagnosis and management of vein of Galen “Evolution of treatment options for vein of aneurysm: review illustrated by a case report,” Galen malformations: a review,” Journal of Journal de Gynecologie Obstetrique et Biologie Neurosurgery, vol. 6, no. 5, pp. 444–451, 2010. de la Reproduction, vol. 34, no. 6, pp. 613–619, 2005. 6. P. L. Lasjaunias, S. M. Chng, M. Sachet, H. Alvarez, G. Rodesch, and R. Garcia-Monaco, 11. P. J. Mitchell, J. V. Rosenfeld, P. Dargaville et al., “The management of vein of Galen aneurysmal “Endovascular management of vein of Galen malformations,” Neurosurgery, vol. 59, no. 5, aneurysmal malformations presenting in the pp. S184–S194, 2006. neonatal period,” American Journal of Neuroradiology, vol. 22, no. 7, pp. 1403–1409, 7. M. Pearl, J. Gomez, L. Gregg, and P. Gailloud, 2001.

6 6 Vol 18 No 1 January – JUNE 2018 12. H. Alvarez, R. G. Monaco, G. Rodesch, M. Sachet, the vein of Galen: the role of prenatal diagnosis T. Krings, and P. Lasjaunias, “Vein of Galen and trans-arterial embolization,” aneurysmal malformations,” Neuroimaging Neuroradiology, vol. 34, no. 5, pp. 457–459, 1992. Clinics of North America, vol. 17, no. 2, pp. 18. G. Rodesch, F. Hui, H. Alvarez, A. Tanaka, and 189– 206, 2007. P. Lasjaunias, “Prognosis of antenatally 13. I. H. Johnston, I. R. Whittle, M. Besser, and M. diagnosed vein of Galen aneurysmal K. Morgan, “Vein of Galen malformation: malformations,” Child’s Nervous System, vol. diagnosis and management,” Neurosurgery, vol. 10, no. 2, pp. 79– 83, 1994. 20, no. 5, pp. 747–758, 1987. 19. B. V. Jones, W. S. Ball, T. A. Tomsick, J. Millard, 14. N. McSweeney, S. Brew, S. Bhate, T. Cox, D. J. and K. R. Crone, “Vein of Galen aneurysmal Roebuck, and V. Ganesan, “Management and malformation: diagnosis and treatment of 13 outcome of vein of Galen malformation,” children with extended clinical followup,” Archives of Disease in Childhood, vol. 95, no. American Journal of Neuroradiology, vol. 23, 11, pp. 903–909, 2010. no. 10, pp. 1717–1724, 2002. 15. A. Foran, V. Donohue, P. McParland et al., “Vein 20. H. J. Fullerton, A. R. Aminoff, D. M. Ferriero, of Galen aneurysm malformation (VGAM): N. Gupta, and C. F. Dowd, closing the management loop,” Irish Medical “Neurodevelopmental outcome after Journal, vol. 97, no. 1, pp. 8–10, 2004. endovascular treatment of vein of Galen 16. G. P. Frawley, P. A. Dargaville, P. J. Mitchell, B. M. malformations,” Neurology, vol. 61, no. 10, pp. Tress, and P. Loughnan, “Clinical course and 1386–1390, 2003. medical management of neonates with severe 21. J. A. Ellis, L. Orr, P. C. Ii, R. C. Anderson, N. A. cardiac failure related to vein of Galen Feldstein, and P. M. Meyers, “Cognitive and malformation,” Archives of Disease in functional status after vein of Galen aneurysmal Childhood, vol. 87, no. 2, pp. F144–F149, 2002. malformation endovascular occlusion,” World 17. Y. Yamashita, T. Abe, N. Ohara et al., “Successful Journal of Radiology, vol. 4, no. 3, pp. 83–89, treatment of neonatal aneurysmal dilatation of 2012

MRI Department, Institute of Child Health, Calcutta

How long it is open? It is open from 9 am to 7pm on weekdays. On Sunday, it is open from 9am to 1pm. What is the usual time required for MRI scan? About 30 minutes. How an appointment is made? It is usually done at the reception of MRI department by personal visit or over telephone. Telephone No.s (033)2289-3526 and (033)6526-6969. What preparation is needed for MRI? Usually no preparation is needed. For MRCP study 4-6 hours fasting is needed. For children, oral sedation is usually required. In some hyperactive, restless patients anesthesia is needed. We have fully equipped setup for anesthesia and extremely competent anesthetist for such patients. About 6 hours of fasting is needed prior to anesthesia.

Annals of ICH, Calcutta 6 7 Journal Scan Rajiv Sinha Professor and Head Pediatric Nephrology Unit, Institute of Child Health, Kolkata

1. Note the change!!! upward were more likely to be overweight Sharma AK, Metzger DL, Rodd CJ. or obese, with higher z scores for weight, waist Prevalence and Severity of High Blood circumference, and body mass index. The Pressure Among Children Based on the 2017 prevalence of abnormal laboratory test results American Academy of Pediatrics Guidelines. was also increased, with adverse lipid profiles JAMA Pediatr. 2018 Jun 1; 172 (6):557-565 and increased hemoglobin A1c levels (prediabetes). Clustering of cardiovascular risk The effect of recent change in AAP blood factors in otherwise healthy US children pressure guideline: Based on the new 2017 suggests that those BP reclassified represent a blood pressure guidelines, the prevalence of high-risk population whose cardiovascular risk high blood pressure (BP) among adults has may previously have been underestimated. increased from 32% to 46%. The current study tried to assess the impact of its change in 2. Choose your poison!!! paediatric practice in comparison to the 2004 Mitra S, Florez ID, Tamayo ME, Mbuagbaw fourth report. This study applied both sets L, Vanniyasingam T, Veroniki AA, Zea AM, of guidelines to classify BP in 15647 generally Zhang Y, Sadeghirad B, Thabane L. healthy, low-risk children aged 5 to 18 years Association of Placebo, Indomethacin, from National Health and Nutrition Ibuprofen, and Acetaminophen with closure Examination Surveys (from January 1, 1999, of hemodynamically significant Patent Ductus to December 31, 2014). Among the 15647 Arteriosus in preterm infants: A Systematic children in the study (7799 girls and 7848 boys; Review and Meta-analysis. JAMA. 2018 Mar mean [SD] age, 13.4 [2.8] years), based on the 27;319 (12):1221-1238. American Academy of Pediatrics guidelines, Ibuprofen seems to have the edge in closing the estimated (weighted) population PDA: Although there are increasing emphasis prevalence of elevated BP increased from on conservative management of patent ductus 11.8% (95% CI, 11.1%-13.0%) to 14.2% arteriosus (PDA) in preterm infants, different (95% CI, 13.4%-15.0%). Overall, 905 of pharmaco-therapeutic interventions are still 15584 children (5.8%) had newly diagnosed often required for those developing a hypertension (n=381) or a worsening in clinical hemodynamically significant PDA. The meta- stage (n=524), which represents a substantial analysis was conducted to estimate the relative increase in disease burden for the health care likelihood of hemodynamically significant system. Children whose BP was reclassified PDA closure with common pharmaco-

6 8 Vol 18 No 1 January – JUNE 2018 therapeutic interventions and to compare proton pump inhibitor users (RR = 1.34; 95% adverse event rates. In 68 randomized clinical CI 1.18-1.52; I2 = 46%; P < .00001) and trials of 4802 infants, 14 different variations histamine-2 receptor antagonist users (RR = of indomethacin, ibuprofen, or 1.57; 95% CI 1.46-1.69; I2 = 0%; P < .00001). acetaminophen were used as treatment Although none of the studies adjusted for all modalities. The overall PDA closure rate was the known confounding factors the publication 67.4% (2867 of 4256 infants). Based on the should caution us to a reflex use of acid ranking statistics, a high dose of oral ibuprofen suppressive drugs among pregnant women. ranked as the best pharmaco-therapeutic 4. A biomarker for brain injury!!! option for PDA closure (mean surface under Oris C, Pereira B, Durif J, Simon-Pimmel J, the cumulative ranking [SUCRA] curve, 0.89 Castellani C, Manzano S, Sapin V, Bouvier D. [SD, 0.12]) and to prevent surgical PDA The Biomarker S100B and Mild Traumatic ligation (mean SUCRA, 0.98 [SD, 0.08]). There Brain Injury: A Meta-analysis. was no significant difference in the odds of mortality, necrotizing enterocolitis, or Pediatrics. 2018 Jun;141(6). pii: e20180037. doi: intraventricular hemorrhage with use of 10.1542/peds.2018-0037. placebo or no treatment compared with any Can we reduce need for CT scan for mild of the other treatment modalities. traumatic brain injury? 3. Better to suffer from acidity? S100B has been noted as a useful biomarker Lai T, Wu M, Liu J, Luo M, He L, Wang X, in the management of mild traumatic brain Wu B, Ying S, Chen Z, Li W, Shen H. Acid- injury (mTBI) in adults but its efficacy as a Suppressive drug use during pregnancy and biomarker in children needs further the risk of childhood asthma: A Meta-analysis. exploration. This meta-analysis was conducted Pediatrics. 2018 Feb;141(2). pii: e20170889. to assess the prognostic value of S100B in doi: 10.1542/peds.2017-0889 predicting intracerebral lesions in children after Antenatal exposure to acid suppressive drugs mTBI. Of 1030 articles screened, 8 studies increases risk of childhood asthma: A met the inclusion criteria. The overall pooled systematic review and meta-analysis was sensitivity and specificity were 100% (95% conducted to assess the association between confidence interval [CI]: 98%-100%) and 34% acid-suppressive drug exposure during (95% CI: 30%-38%), respectively. Only 1 child pregnancy and childhood asthma. 556 articles had a low S100B level and a positive CT scan were screened and 8 population-based studies result without clinically important traumatic were included in the final analyses. The pooled brain injury. In conclusion S100B serum analysis revealed that acid-suppressive drug use analysis as a part of the clinical routine could in pregnancy was associated with an increased significantly reduce the number of CT scans risk of asthma in childhood (relative risk [RR] performed on children with mTBI. Sampling = 1.45; 95% confidence interval [CI] 1.35- should take place within 3 hours of trauma 1.56; I2 = 0%; P < .00001). The overall risk and cut off levels should be based on pediatric of asthma in childhood increased among reference ranges.

Annals of ICH, Calcutta 6 9 5. More is not always better!!! assess the role of frusemide in bone fracture Rosendahl J, Valkama S, Holmlund-Suila E, in children with congenital heart disease. There Enlund-Cerullo M, Hauta-Alus H, Helve O, were 3 groups of children, one group was a Hytinantti T, Levälahti E, Kajantie E, furosemide-adherent group (medication Viljakainen H, Mäkitie O, Andersson S. Effect possession ratio of 70%), one was a of Higher vs Standard Dosage of Vitamin furosemide-non adherent group (medication D3 Supplementation on Bone Strength and possession ratio of <70%) and the third group Infection in Healthy Infants: A Randomized was non furosemide group All of them were Clinical Trial. 2018 May 29. doi: 10.1001/ below 12 years with congenital heart disease, jamapediatrics.2018.0602. cardiomyopathy, or heart failure. The incidence Higher dose of vitamin D gives no added of fractures was 9.1% highest in the advantage on bone strength or infection: A furosemide-adherent group and 7.2% in the randomised controlled trial was done in furosemide-non-adherent group and 5.0% in Finland to assess the outcomes of bone non-furosemide group. Even on logistic strength and incidence of parent-reported regression incidence remained higher in both infections at 24 months in 925 healthy children. furosemide adherent and non adherent group 489 infants received daily oral vitamin D3 (Furosemide-adherent OR of 1.9 [95% CI, supplementation of 400 IU and 486 infants 1.17-2.98; P=.009]; furosemide non-adherent received 1200 IU from age 2 weeks to 24 OR of 1.5 [95% CI, 1.10-2.14] P=.01). They months. Apart from the higher mean concluded that even with non-consistent 25(OH)D concentration in the 1200-IU group dosing, furosemide was associated with an no difference was found in bone mineral increased risk of bone fractures in children content / density among the group. There was with congenital heart disease. In the Cox also no difference in the incidence of infection. proportional hazard model, the risk of They concluded that daily supplementation fractures for the furosemide-adherent group with 400 IU vitamin D3 is adequate in was significantly higher compared with the no maintaining vitamin D sufficiency in children furosemide group (HR, 1.6; 95% CI, 1.00- younger than 2 years. 2.42; P=.04). 6. Frusemide – Use with caution!!! 7. Oiling does not always ensure a Heo JH, Rascati KL, Lopez KN, Moffett BS. positive response!!! Increased fracture risk with furosemide use Santer M, Ridd MJ, Francis NA, Stuart B, in children with congenital heart disease. J Rumsby K, Chorozoglou M, Becque T, Pediatr. 2018 May 9. pii: S0022- Roberts A, Liddiard L, Nollett C, Hooper J, 3476(18)30489-X. doi: 10.1016/ Prude M, Wood W, Thomas KS, Thomas- j.jpeds.2018.03.077. Jones E, Williams HC, Little P. Emollient bath Furosemide can make bones fragile: A additives for the treatment of childhood retrospective cohort study was done from the eczema (BATHE): multicentre pragmatic 2008-2014 using Texas Medicaid databases to parallel group randomised controlled trial of

7 0 Vol 18 No 1 January – JUNE 2018 clinical and cost effectiveness. BMJ. 2018 May the surgeries before 9 yrs of age and followed 3;361:k1332. doi: 10.1136/bmj.k1332. up at least 10 years after operation or up to Bath Emollients May Not Help Children with 30 yrs of their age. They showed that Eczema: A randomized study was done to adenoidectomy and tonsillectomy were see the effectiveness of emollient bath to associated with a 2- to 3-fold increase in improve eczema symptoms in children. Nearly diseases of the upper respiratory tract 500 children aged 1 to 11 years with infection. More risks were found after moderate-to-severe atopic dermatitis were adenotonsillectomy. Smaller increases in risks randomized to receive either standard care i.e. for infectious and allergic diseases were also leave-on emollient and topical corticosteroids found. Although the authors do admit that as needed or standard care plus a choice of they might have missed some confounding one of three emollients added to the child's factors it warns us about the adverse bath, including Aveeno, Oilatum, or Balneum. consequences of removal of tonsils and At the end of 16 weeks, the primary outcome adenoids. with eczema severity score was similar in the 9. Fluid regimen in DKA- does it matter? bath emollient and control groups. There were Kuppermann N, Ghetti S, Schunk JE, Stoner statistically significant improvements among MJ, Rewers A, McManemy JK, Myers SR, children under age 5 and those who had five Nigrovic LE, Garro A, Brown KM, Quayle or more baths a week, but these were not KS, Trainor JL, Tzimenatos L, Bennett JE, deemed clinically significant by the authors. DePiero AD, Kwok MY, Perry CS 3rd, Olsen 8. Think before you take out the knife!!! CS, Casper TC, Dean JM, Glaser NS; Byars SG, Stearns SC, Boomsma JJ. PECARN DKA FLUID Study Group. Association of long-term risk of respiratory, Clinical Trial of Fluid Infusion Rates for allergic, and infectious diseases with removal Pediatric Diabetic Ketoacidosis. N Engl J of adenoids and tonsils in childhood. JAMA Med. 2018 Jun 14;378 (24):2275-2287. Otolaryngol Head Neck Surg. 2018 Jun 7. doi: Neither rate of administration nor the sodium 10.1001/jamaoto.2018.0614 chloride content of intravenous fluids has any Does Removing Tonsils, Adenoids, or Both significant effect on the neurologic outcomes in Childhood Increase Illness Later? As tonsil in children with Diabetic ketoacidosis (DKA). and adenoid play important roles in the DKA in children is one of the major illnesses function of the immune system. , it is which can cause brain injuries. There is important to know the long-term controversy regarding the contributing factor consequences of removal of tonsil and for these injuries. A 13-center, randomized, adenoid in childhood. In this study from controlled trial was done to see whether the Denmark almost 1.2 million children were rate of administration and the sodium reviewed, of whom 17460 had chloride content of intravenous fluids have adenoidectomy, 11830 tonsillectomy, and any role on the neurologic outcomes in children 31377 adenotonsillectomy. They underwent with DKA. The primary outcome considered

Annals of ICH, Calcutta 7 1 as a decline in mental status according to Options for GERD in pre-terms: Glasgow Coma Scale scores during treatment Pharmacologic agents "should be used and the secondary outcomes included clinically sparingly" in preterm infants with apparent brain injury and short-term memory gastroesophageal reflux, according to new during treatment and memory and IQ at 2 guidance published in Pediatrics. to 6 months after recovery. Children were The American Academy of Pediatrics also randomly distributed to one of four treatment recommended the following for groups in a 2-by-2 factorial design depending gastroesophageal reflux, which is nearly on rapid or slow rate of administration and 0.9% or 0.45% sodium chloride content). No universal among preterm infants: significant differences were found with respect • The signs of reflux (including feeding to the magnitude, duration and the percentage intolerance or aversion, poor weight gain, of episodes of the Glasgow Coma Scale frequent regurgitation, apnea, desaturation, score declined to below 14. There was also bradycardia, irritability, and perceived no difference with respect to the results of postprandial discomfort) generally the tests of short-term memory, clinically improve over time without treatment. apparent brain injury during treatment and Memory and IQ scores after recovery from • Non-pharmacologic treatments (head DKA also did not differ significantly among elevation and manipulating infant feeding) the groups. Hence the study concluded that have not been proven to reduce reflux the rate of administration and the sodium signs among preterm infants. chloride content of intravenous fluids do not • Pharmacologic agents also lack strong have any significant effect on the neurologic evidence of efficacy but do have evidence outcomes in children with DKA. of potential harm, resulting in the authors 10. Stuck between a rock and a hard to suggest that"these agents should be place!!! used sparingly, if at all, in preterm infants." Eichenwald EC; COMMITTEE ON FETUS AND NEWBORN. Diagnosis and • Before discharge, parents should be Management of Gastroesophageal Reflux in educated on sleep safety, including not Preterm Infants. Pediatrics. 2018 Jun 18. pii: using devices designed to elevate the e20181061. doi: 10.1542/peds.2018-1061. infant's head in the crib. Immunization Clinic Immunisation Clinic of the Institute of Child Health offers service of not only EPI Vaccines, but also of all newer vaccines at reasonable cost. Thousands of children are benefitted by the service of this clinic.

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