Clinic Consult

Childhood Diarrhea

PRELIMS.indd 1 18-12-2013 14:38:15 PRELIMS.indd 2 18-12-2013 14:38:15 Clinic Consult

Childhood Diarrhea

Authors Ajay Kalra Md Dch Mnams Fiap Erstwhile Professor S.N. Medical College Agra 282 002, Uttar Pradesh, India

Vipin M Vashishtha MD FIAP Director & Consultant Pediatrician Mangla Hospital & Research Center Bijnor 246 701, Uttar Pradesh, India

Jaypee Brothers Medical Publishers (P) Ltd. New Delhi • London • Philadelphia • Panama

PRELIMS.indd 3 18-12-2013 14:38:15 Jaypee Brothers Medical Publishers (P) Ltd

Headquarters Jaypee Brothers Medical Publishers (P) Ltd 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected] Overseas Offices J.P. Medical Ltd Jaypee-Highlights Medical Publishers Inc 83 Victoria Street, London City of Knowledge, Bld. 237, Clayton SW1H 0HW (UK) Panama City, Panama Phone: +44-2031708910 Phone: +1 507-301-0496 Fax: +02-03-0086180 Fax: +1 507-301-0499 Email: [email protected] Email: [email protected] Jaypee Medical Inc Jaypee Brothers Medical Publishers (P) Ltd The Bourse 17/1-B Babar Road, Block-B, Shaymali 111 South Independence Mall East Mohammadpur, Dhaka-1207 Suite 835, Philadelphia, PA 19106, USA Bangladesh Phone: +1 267-519-9789 Mobile: +08801912003485 Email: [email protected] Email: [email protected] Jaypee Brothers Medical Publishers (P) Ltd Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 Email: [email protected] Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2014, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. Inquiries for bulk sales may be solicited at: [email protected] Clinic Consult: Childhood Diarrhea First Edition: 2014 ISBN 978-93-5152-122-8

Printed at

PRELIMS.indd 4 18-12-2013 14:38:16 Preface

Diarrhea remains the most common problem of children in developing countries. Yet, it is the one most unjudiciously treated. This underscores the need to keep oneself updated on the subject and follow rationale mode of management. We hope that this Clinic Consult will help practitioners to be able to do so.

Ajay Kalra Vipin M Vashishtha

PRELIMS.indd 5 18-12-2013 14:38:16 PRELIMS.indd 6 18-12-2013 14:38:16 Acknowledgements

We have consulted various resource literature to write this book. We are grateful to all those who are mentioned in the bibliography. We are also grateful to the publishers for the wonderful job done.

PRELIMS.indd 7 18-12-2013 14:38:16 PRELIMS.indd 8 18-12-2013 14:38:16 Contents

Preface v Acknowledgements vii

Chapter 1 Diarrhea in Children 1 Chapter 2 Causes and Mechanisms of Diarrhea 5 Chapter 3 Pathogenesis of Diarrhea 10 Chapter 4 Clinical Diagnosis of Diarrhea 14 Chapter 5 Physical Examination 19 Chapter 6 Laboratory Investigations 25 Chapter 7 Management of Acute Diarrhea 28 Chapter 8 Drug Therapy in Diarrhea 42

PRELIMS.indd 9 18-12-2013 14:38:16 Clinic Consult: Childhood Diarrhea

Chapter 9 Dietary Management 54 Chapter 10 Persistent/Protracted/Recurrent/Chronic Diarrhea 57 Chapter 11 Celiac Disease 68 Chapter 12 Lactose Intolerance 70 Chapter 13 Cow’s Milk Protein Intolerance 74 Chapter 14 Vaccines Against Diarrheal Diseases 76

Bibliography 81

Normal lactose digestion Lactose intolerance

x

PRELIMS.indd 10 18-12-2013 14:38:16 CHAPTER 1

Diarrhea in Children

Introduction Diarrhea is a leading cause of morbidity and mortality in developing countries. Each year in developing countries, roughly 4 billion episodes of acute diarrhea take place. In India, a child suffers, on an average, of 10–15 episodes of diarrhea in the first 5 years of life. Of these, 3–6 episodes (average 4.2) may occur in the very first year of life, especially in the urban slums and rural areas. It is responsible for nearly 2 million deaths of children below 5 years age every year in the developing world. The surface area of intestinal mucosa of a child from where the diarrheal fluids are secreted is fairly large. Therefore, a child may lose almost as much water and electrolytes from the body during the episode of diarrhea as an adult. Loss of 1 liter of fluid from the body of a child weighing 7 kg may be more dangerous compared with a similar depletion from an adult of 70 kg weight. Out of all cases of diarrhea, nearly 2–3% would have a significant disturbance in the electrolyte balance and acid base status of the body and this may prove fatal, if fluids and electrolytes are not replaced immediately. Diarrhea has been shown to have significant impact on nutrition. Even a brief episode of diarrhea leads to the loss of 1–2% of body

ch-01.indd 1 18-12-2013 14:31:00 Clinic Consult: Childhood Diarrhea

weight per day. Infants and young children in developing countries are sick for nearly 30 days per year because of diarrhea. Therefore, such creeping deficit may accumulate to become a major nutritional hazard. If diarrhea becomes unusually prolonged, or is recurrent, the child further becomes severely malnourished. Moreover, the appetite is impaired, and food is often withheld from the child by the mother due to the belief that starvation may provide rest to the bowel and thus promote early recovery. Further, atrophy of the intestinal epithelium in cases of malnutrition causes malabsorption and accentuates malnutrition. A vicious cycle of diarrhea–malnutrition–diarrhea sets in, contributing to a large majority of early childhood deaths either directly or indirectly.

Definition When a person has watery motions, it is called diarrhea. Diarrhea does not always mean many motions. Even one watery motion can be diarrhea. This is also regardless of its cause, its color, or any illness associated with it. Diarrhea can be very dangerous, especially in very small or weak children. This is because diarrhea leads to dehydration, which may cause death. That is why one must start treating a child for diarrhea as soon as the child passes even one watery motion. Young infants usually pass about 5 g of stool per kg of body weight per day, while diarrhea results in stool output greater than 10 g/kg/day.

WHAT IS NOT DIARRHEA? • Frequent semiformed or watery greenish yellow stools in the initial days of life (transitional stools). Due to some weight

2

ch-01.indd 2 18-12-2013 14:31:00 Diarrhea in Children

loss, they are often thought of as diarrhea. It is self-limiting and requires no treatment • Formed or pasty stools frequently passed in exclusively breastfed babies • Passing a stool immediately after feed by infants 3–6 months of age: It is due to exaggerated gastrocolic pattern, quite normal at this stage and requires no treatment

CLASSIFICATION OF DIARRHEA Acute diarrhea: It is passage of several watery and loose stools in a day which generally terminate within 7 days (only rarely 14–28 days).

Persistent diarrhea: World Health Organization (WHO) defines this as a diarrheal illness, which begins acutely and lasts for 14 days or more. More than 60% episodes occur in infants less than 6 months and 90% before 1 year of age.

Chronic diarrhea: It is diarrhea of more insidious onset with stools, which are less watery in nature and semisolid. Their frequency may be four to five times per day. It is seen more in children above 3 years of age.

Dysentery: It is presence of visible blood in stool. It is usually accompanied by pus and abdominal cramps and fever. Shigella is the most common cause requiring treatment with antibiotics. Acute infective diarrhea may be both “noninflammatory” or “inflammatory”. Noninflammatory diarrhea is due to enterotoxin produced by bacteria, destruction of villus (surface cells) by viruses, or adherence by parasites. Diarrhea may be inflammatory due to bacteria that invade intestine directly or produce cytotoxins.

3

ch-01.indd 3 18-12-2013 14:31:00 Clinic Consult: Childhood Diarrhea

key messages

‰‰ Diarrhea is a leading cause of morbidity and mortality in children in the developing world ‰‰ It can lead to dehydration and associated acid–base disturbances which, if not recognized and treated, can prove fatal ‰‰ Recurrent/prolonged diarrhea can cause malnutrition and failure to thrive ‰‰ Many normal physiological stooling patterns are confused with diarrhea and treated unnecessarily.

4

ch-01.indd 4 18-12-2013 14:31:01 CHAPTER 2 Causes and Mechanisms of Diarrhea

CAUSES OF DIARRHEA Acute diarrhea in young children is mostly due to infections with a wide variety of organisms. About 30–40% of diarrheal episodes are due to viruses, of which rotavirus is the most common. Nearly 50% are due to bacterial infections of the gut, of which Shigella is the most common. However, the presence of bacteria in the stools does not by itself mean that these bacteria are the causative agents. Table 1 gives a list of causes of acute diarrhea. The exact incidence of microbes may vary from place to place and at different periods of the year. Table 2 provides the causes of microbial diarrhea in India.

MECHANISM OF DIARRHEA • Bacteria cause diarrhea by two distinct mechanisms, viz., through the action of toxin and direct invasion of the intestinal mucosa. 1. Diarrhea due to toxins: In young children, 30–40% of all cases of diarrhea can be attributed to toxin producing strains of Escherichia coli—enterotoxigenic E. coli (ETEC) [enteropathogenic E. coli (EPEC)—do not liberate any toxins]. These as well as cholerae vibrio do not actually invade the

ch-02.indd 5 18-12-2013 14:31:23 Clinic Consult: Childhood Diarrhea

Table 1 Various causes of acute diarrhea Gastrointestinal infection Viral Rotavirus, Norwalk virus, Astrovirus, enteric adenovirus, cytomegalovirus

Bacterial Enterotoxigenic Escherichia coli, enteropathogenic E. coli, Shigella, Salmonella, Vibrio cholerae, Clostridium difficile, Staphylococcus aureus, Campylobacter, Yersinia

Parasite Giardia lamblia, Entamoeba histolytica, Hymenolepis nana, Cryptosporidium parvum

Fungal Candida Food Lactose intolerance, Cow’s milk protein intolerance, intolerance Gluten intolerance Systemic Otitis media, pneumonia, meningitis, urinary tract infection infections

Table 2 Etiology of acute diarrhea Pathogen Incidence (%) Rotavirus 25–30

Enterotoxigenic Escherichia coli 20 Shigella 5–10 Enteropathogenic E. coli, locally adherent E. coli, 5–7 Campylobacter, Salmonella Giardia lamblia, Entamoeba histolytica <2 Vibrio cholerae 5–10

6

ch-02.indd 6 18-12-2013 14:31:24 Causes and Mechanisms of Diarrhea

intestinal mucosa and there is no evidence of inflammatory response in the gut. Toxins produced by these organisms stimulate the enzyme adenyl cyclase in the enterocytes, which increases the production of cyclic adenosine monophosphate production (AMP). The latter promotes active losses of electrolytes and water from the intestinal cells. ETEC strains release heat-labile (LT) and/or heat-stable enterotoxin (ST). LT enterotoxin released by ETEC is similar to the cholera toxin structure and mode of action. ST causes diarrhea by stimulating guanyate cyclase with an associated increase in cyclic guanosine monophosphate (GMP) and causes severe secretory diarrhea. Antibiotics are not helpful in these cases. The reason for giving antibiotics in cholera infection is to kill the organisms which are likely to be shed from the intestine and lead to diarrhea in the contacts. 2. Diarrhea by direct invasion: In 5–10% of all cases of diarrhea, the microbes, such as Shigella invade the mucosal cells, proliferate, and cause necrosis. The necrosis results in passage of blood and mucus in the stools, giving rise to what is called “dysentery”. Infection with these organisms needs to be managed with antibiotics. Some strains of Shigella may liberate exotoxins, which cause severe systemic toxemia or enterotoxin similar to ETEC and then present with watery diarrhea. Campylobacter jejuni (Helicobacter pylori) invades the intestinal mucosa and is isolated in 5–10% of diarrheal cases. Nontyphoid Salmonella are an infrequent cause of diarrhea, especially in immunocompromised infants. It may cause severe morbidity and may end fatally due to systemic infection.

7

ch-02.indd 7 18-12-2013 14:31:24 Clinic Consult: Childhood Diarrhea

• Rotavirus causes jejunal mucosal damage, which results in villous atrophy and interruption in absorptive mechanisms. As a result of this, lactase enzyme, which is maximally present in superficial layer of villi, is affected and transient lactose intolerance occurs. Resulting diarrhea is severe and watery and usually associated with vomiting. Maximum mucosal damage is at the time of onset of illness. Recovery starts within 24–36 hours (Figure 1) • Systemic infections can also cause diarrhea and vomiting mimicking an attack of acute gastroenteritis. This is more commonly seen in infants and is often labeled as parenteral diarrhea. It is to be treated with the antibiotics targeted at the primary systemic infection • Infestations with Entamoeba histolytica and Giardia lamblia result in subacute and chronic illness rather than acute diarrhea. Presence of intestinal helminthes in stools of cases of acute diarrhea merely reflects their high prevalence in the population.

Normal lactose digestion Lactose intolerance

Figure 1 Lactose intolerance. Source: ©2007, Laurence S Bailen, MD.

8

ch-02.indd 8 18-12-2013 14:31:24 Causes and Mechanisms of Diarrhea

Plasmodium falciparum malaria has often been implicated as a cause of acute diarrhea in tropical countries • Food intolerance is illustrated best by the example of intolerance of gluten protein in wheat. It is due to inability to metabolize or absorb the substance or due to hypersensitivity to the particular protein. The resultant immune-mediated damage to the small bowel mucosa causes diarrhea. Complete withdrawal of the offending protein from the diet helps in treatment.

key messages

‰‰ Gut infections, intolerance to food constituents, and systemic infections are common causes of diarrhea ‰‰ Organisms causing diarrhea can be viral, bacterial, parasitic, or fungal ‰‰ Rotavirus is the most common organism causing diarrhea ‰‰ Most pathogens mediate their effects either by toxin production, or mucosal invasion, or immune-mediated mucosal damage.

9

ch-02.indd 9 18-12-2013 14:31:24 CHAPTER 3

Pathogenesis of Diarrhea

The greatest volume of intestinal water is absorbed in the small bowel. Therefore, disorders that interfere with absorption in the small bowel tend to produce voluminous diarrhea. The colon concentrates intestinal contents against a high osmotic gradient. Hence, disorders compromising colonic absorption produce lower volume diarrhea. Dysentery (i.e., small volume, frequent blood stools with mucus, tenesmus, and urgency) is the predominant symptom of colitis. The basis for all diarrheas is disturbed solute transport. Water movement across intestinal membranes is passive and is determined by both active and passive fluxes of solutes, particularly sodium chloride and glucose. The pathogenesis of most episodes of diarrhea can be explained by secretory, osmotic, or motility abnormalities or a combination of these (Table 1).

Secretory Diarrhea The classic example of secretory diarrhea is that induced by cholera and Escherichia coli enterotoxins. These enterotoxins bind to a specific enterocyte surface receptor (the monosialoganglioside GM1) and a fragment of the toxin then enters the cell. Here it interacts with

ch-03.indd 10 18-12-2013 14:31:43 Pathogenesis of Diarrhea Blood, Persists during fasting (NPO) No leukocytes in stools Stops with fasting No leukocytes in stools Infection may also contribute to increased motility Possible bacterial overgrowth Dysentery: mucus and WBCs Comment Cholera toxigenic Escherichia coli Congenital chloride diarrhea Clostridium difficile Lactase deficiency Glucose galactose malabsorption Lactulose, laxative abuse Irritable bowel syndrome Thyrotoxicosis Pseudo-obstruction Blind loop Shigella Salmonella Amebiasis Campylobacter Rotavirus enteritis Examples ) + + K + ) + + K + Watery Acidic + reducing substances Increased osmolality Osmosis >2x (Na Loose to normal appearing stool Stimulated by gastrocolic reflex Loose to normal appearing stool Blood and increased WBCs in stool Stool examination Watery Normal osmolality osmols: 2x (Na Maldigestion Transport defects Ingestion of unabsorbable solute Decreased transit time Stasis (bacterial overgrowth) Defect in neuromuscular units Inflammation Decreased mucosal surface area and/or chronic reabsorption Increased motility Defect Decreased absorption Increased secretion Electrolyte transport , potassium; NPO, nil per os; WBCs, white blood cells. + , sodium; K + Osmotic Motility: Increased motility Decreased motility Mucosal inflammation Pathogenesis of diarrhea Secretory Primary genesis T able 1 Na

11

ch-03.indd 11 18-12-2013 14:31:43 Clinic Consult: Childhood Diarrhea

a stimulatory G-protein and activates the enzyme adenylate cyclase on the basolateral membrane. This increases intracellular cyclic adenosine monophosphate production (AMP), which promotes active losses of electrolytes and water from intestinal cells.

Osmotic Diarrhea Osmotic diarrhea is caused by nonabsorbable solutes present in the gastrointestinal tract. Lactose intolerance is the classic example of osmotic diarrhea. Because of deficiency of lactase enzyme, lactose is not absorbed in the small intestine and reaches the colon intact. Examples are diarrhea caused by rotavirus and enteropathogenic E. coli (EPEC) (Table 2).

Table 2 Mechanism of action of enteropathogens Organisms which adhere to the Enterotoxigenic Escherichia coli, mucosa and produce enterotoxins Vibrio cholerae (secretory diarrhea, no inflammation of the gut) Organisms which damage the brush Enteropathogenic E. coli (some of border and its enzymes (cause these are enteroadherent), rotavirus carbohydrate malabsorption) Organisms that invade the mucosa Shigella, enteroinvasive E. coli and proliferate in the intestinal epithelium Organisms which proliferate in Nontyphoid Salmonella, the lamina propria and invade the Campylobacter jejuni, Yersinia mesenteric lymph nodes enterocolitica Disordered small intestinal epithelial Rotavirus renewal

12

ch-03.indd 12 18-12-2013 14:31:43 Pathogenesis of Diarrhea

key messages

‰‰ Most enteropathogens can cause diarrhea by more than one mechanism ‰‰ The basis for all diarrhea is disturbed solute and water transport ‰‰ Pathogenesis of diarrhea can be classified as secretory, osmotic, dysfunctional motility, or mucosal inflammatory.

13

ch-03.indd 13 18-12-2013 14:31:43 CHAPTER 4 Clinical Diagnosis of Diarrhea

Quite often, it is possible to diagnose the cause of diarrhea on clinical grounds and without any investigations. The following clinical parameters may help.

HISTORY • The age of child is important as many illnesses are typically present at certain ages. Rotavirus diarrhea occurs in early infancy. Norwalk virus infection occurs in slightly older infants and preschool children • It might be possible to distinguish inflammatory cause from non­­inflammatory cause. Inflammatory disorders typically cause extra­intestinal symptoms, such as fever, arthritis, anemia, leukocytosis, and/or blood or mucus in the stool. Patients with noninflammatory disorders generally have milder symptoms and would not have mucus in the stool • Small intestinal pathology usually results in a large volume of diarrhea, and may also result in malabsorption in one or more nutrients. Large bowel pathology usually results in smaller volume of diarrhea, unless there is a secretary element to the diarrhea. Inflammation of the large intestine is more likely to

ch-04.indd 14 18-12-2013 14:32:01 Clinical Diagnosis of Diarrhea

present with gross blood and mucus in the stool along with symptoms of fecal urgency and tenesmus • Viral diarrhea generally has a short incubation period of 2–5 days. Soon afterward, the virus particles are excreted causing symptoms, such as vomiting, diarrhea, fever, and abdominal cramping. The symptoms usually subside within 7 days • Patients with bacterial gastroenteritis often present with fever, abdominal pain, and blood or mucus in the stool. The diarrhea is typically self-limited and resolves within 10 days. However, several pathogens like Salmonella, Shigella, Yersinia enterocolitica, and Campylobacter jejuni can cause persistent diarrhea. Clostridium difficile produces a toxin that can cause pseudomembranous colitis. It is typically associated with anti­ biotic administration but can occur spontaneously as well • Presence of other medical problems can also give a clue to the etiology of diarrhea, viz., respiratory tract infection, otitis media, urinary tract infection (UTI) or some other acquired immunodeficiency syndrome, or other immune deficiency.

FEVER Presence of fever in a child with acute diarrhea can provide some information and may indicate need for special evaluation. • In rotavirus diarrhea, the fever is occasionally of high grade but the child does not look toxic • In shigellosis, the child has toxemia besides fever as gastrointestinal infections (except Salmonella rarely caused fever beyond 36–48 hours; every child with fever of more than 48 hours should be investigated) • In a child with persistent fever, diarrhea is only of a secondary importance. Onset of fever preceding the onset of diarrhea

15

ch-04.indd 15 18-12-2013 14:32:01 Clinic Consult: Childhood Diarrhea

may indicate systemic infection and should be accordingly investigated. Parenteral infections cause not only fever but also other symptoms like excessive crying (otitis media, meningitis), respiratory distress (pneumonitis), and dysuria or urinary frequency (UTI).

NAUSEA AND VOMITING IN ACUTE DIARRHEA • These are nonspecific symptoms but vomiting may suggest infection in the upper intestine, such as by enteric viruses, entero­ toxin-producing bacteria, and Giardia and Cryptosporidium • If emesis is not accompanied by fever or the fever is of low grade, then the diarrhea may be due to noninflammatory cause • A child with isolated or persistent vomiting should be considered for an affliction outside the gastrointestinal tract (throat, chest, meninges, liver, urinary tract, etc.) rather than in the gastrointestinal tract itself. Hence, all children with persistent vomiting with or without diarrhea need very careful appraisal for these problems rather than just trying to stop vomiting.

CONSISTENCY AND CONTENT OF STOOLS At times, this may also provide a clue to the cause of diarrhea. On the basis of the type of stools, it has been classified as acute watery diarrhea and acute invasive (bacillary dysentery) diarrhea syndrome.

Watery Diarrhea/Mucoid Diarrhea • Rotavirus and other viral diarrheas

16

ch-04.indd 16 18-12-2013 14:32:01 Clinical Diagnosis of Diarrhea

• Enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae, Campylobacter, enteropathogenic E. coli (EPEC) • Parenteral infections (otitis media, UTI, pneumonia) • Giardia (occasionally) • Early stages of Shigella (rarely).

Invasive Diarrhea (Loose Stools with Blood) • Shigella, enteroinvasive E. coli (EIEC) • Salmonella (nontyphoidal) • Campylobacter • Yersinia.

CAUSATIVE ORGANISM The likely causative organism based on clinical presentation may be as follows: • Infant with severe watery diarrhea, vomiting, and mild-moderate fever: Rotavirus • Similar presentation in older infant/preschool child: Norwalk virus • Child with large, watery stools, vomiting, and severe dehydration: V. cholerae or ETEC • Blood and mucus in stools, fever, abdominal cramps, and tenesmus: Shigella • Small amount of blood in stools: Shigella, Salmonella, Campylo­ bacter, EIEC • Diarrhea in very sick: Looking child who has received broad- spectrum antibiotics—Staphylococcus, Candida, Clostridium • Young infant with perianal excoriations (extending to groins and thighs): Fungal diarrhea/lactose intolerance.

17

ch-04.indd 17 18-12-2013 14:32:01 Clinic Consult: Childhood Diarrhea

CLINICAL MANIFESTATIONS Other clinical manifestations which may also give an idea of the causative organisms are as in table 1.

Table 1 Associated clinical manifestation of different pathogens Manifestation Pathogens Reactive arthritis Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile Guillain-Barre syndrome Campylobacter Acute glomerulonephritis Shigella, Campylobacter, Salmonella IgA nephropathy Campylobacter Erythema nodosum Yersinia, Campylobacter, Salmonella Hemolytic anemia Campylobacter, Yersinia HUS Shigella dysenteriae type 1, Escherichia coli IgA, immunoglobulin A; HUS, hemolytic–uremic syndrome.

key messages

‰‰ Clinical information regarding age of child, stool characteristics, duration, and associated systemic signs and symptoms help in diagnosing the cause ‰‰ Different pathogens may present with myriads of systemic manifestations affecting other organ systems.

18

ch-04.indd 18 18-12-2013 14:32:01 CHAPTER 5

Physical Examination

In a child with acute diarrhea, there are three important assessments that need to be done: 1. Hydration status 2. Nutritional status 3. Presence of parenteral infection, if any.

HYDRATION STATUS This is the singlemost important assessment, as dehydration is the most important cause of morbidity and mortality. Also, the choice of fluid therapy depends on the severity and type of the dehydration. Table 1 gives the features of dehydration in different severities. Weight loss is also a very sensitive indicator, provided the premorbid weight of the child is available.

Restlessness: It is because of increased thirst in a child and indicates some dehydration.

Sunken eyes: It is a very important observation. If in doubt, ask the mother/caretaker whether she or he thinks that the eyes are different, or sunken, as compared to the time when the child was well and did not have diarrhea.

ch-05.indd 19 19-12-2013 12:08:13 Clinic Consult: Childhood Diarrhea

Table 1 Degree of dehydration [World Health Organization (WHO) criteria] Severe Two of the following signs: dehydration Lethargy or unconsciousness Sunken eyes Not able to drink or drinks poorly Skin pinch goes back very slowly (>2 seconds) Some Two of the following signs: dehydration Restless or irritable Sunken eyes Drinks eagerly, thirsty Skin pinch goes back slowly (≤2 seconds) No dehydration Not enough signs to classify as some or severe dehydration

Drinking: A child with some dehydration will eagerly accept fluids. A child who is not eager to drink may not have the dehydration. A child who is unable to feed or who drinks poorly is usually severely ill either due to severe dehydration or another severe illness.

Skin pinch: On pinching the skin, it should be held for a second or two and then released. If it goes back immediately, it is taken as normal. If it remains visible for less than 2 seconds, then it is considered as a slow return and if it remains visible for more than 2 seconds, the return is considered very slow (Figure 1). From management point of view, mild and moderate dehydration can be combined together and termed as “some” dehydration. They can be managed with oral rehydration therapy alone. Children with some dehydration are irritable, but they are alert and keen to drink fluids, and on the other hand, severely dehydrated children are drowsy, apathetic, and unwilling to drink fluids. Change

20

ch-05.indd 20 19-12-2013 12:08:13 Physical Examination

A

B

C Figure 1 Signs of dehydration in a child. Source: World Health Organization. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Illnesses with Limited Resources, illustrated edition. Mumbai, India: Medica Press International; 2005. pp. 122-30.

21

ch-05.indd 21 19-12-2013 12:08:13 Clinic Consult: Childhood Diarrhea

Table 2 Clinical features associated with biochemical imbalance Disturbance Clinical signs Acidosis Breathing increased in depth and rate Alkalosis Breathing decreased in depth and rate Hypokalemia Abdominal distension, paralytic ileus, hypotonia, hyporeflexia, mental apathy, ECG changes (ST depression and flattening of T waves), fibrillation/ paralysis of skeletal muscles, ECG changes Hyperkalemia Tetany, paralytic ileus Hypocalcemia Hypotonia, fecolith Hypercalcemia Tetany, muscular twitching Hypomagnesemia/ CNS depression, hyporeflexia hypermagnesemia ECG, electrocardiogram; CNS, central nervous system.

of sensorium in severe dehydration sets in earlier than the signs and symptoms of shock and should therefore be carefully looked for. Table 2 also provides the clinical features associated with electrolyte and acid imbalance in diarrheal dehydration. This is necessary in order to select a proper fluid and electrolyte therapy.

TYPES OF DEHYDRATION This is of three types: 1. Isotonic dehydration: It occurs when the loss of water and sodium are in the same proportion as found normally in the extracellular fluid. There is a balanced deficit of water and sodium. Normal levels of serum sodium (130–150 mmol/L) and serum osmolality (275–295 mosmol/L) with hypovolemia are due to substantial loss of extracellular fluid.

22

ch-05.indd 22 19-12-2013 12:08:13 Physical Examination

2. Hypernatremic dehydration: This occurs when the loss of water is in excess of sodium loss. It results from ingestion of hypertonic fluids during diarrhea which are not efficiently absorbed and also insufficient intake of water or other low solute drinks. The serum sodium levels are elevated (>150 mmol/L) and serum osmolality is increased (>295 mosmol/L). It presents as thirst out of proportion to the degree of dehydration, extreme irritability and seizures. 3. Hyponatremic dehydration: This occurs when children with diarrhea drink excessive water or hypotonic fluids containing very low amounts of sodium or other solutes. Also, when they are administered 5% dextrose in water as intravenous fluid. Sodium deficiency is greater than that of water and the serum sodium levels are less than 130 mmol/L, while the serum osmolality is less than 275 mOsm/L. Lethargy is a marked feature in these children.

NUTRITIONAL STATUS This is also recognized as an important factor in diarrhea. Children with body weight between 60% and 80% of the expected (mild–to– moderate malnutrition) can be managed like normal malnourished children with extra–attention to nutritional intake. On the other hand, children with severe malnutrition (<60% body weight) having diarrhea would need hospitalization.

PARENTERAL INFECTION As parenteral infection often cause diarrhea in children, especially in infants, it is important to carefully look for these infections. The following features should alert a clinician to the possibility of a parenteral infection:

23

ch-05.indd 23 19-12-2013 12:08:13 Clinic Consult: Childhood Diarrhea

• Fever preceding the onset of diarrhea or persisting for more than 48 hours • Severe malnutrition (body weight <60%) • Lethargy, inactivity in absence of dehydration or persisting even after correction of dehydration • Signs/symptoms of parenteral infection, for example, bulging fontanel, excessive cry, respiratory distress, ear ache, burning micturition, etc. • Dehydration persisting or recurring despite adequate fluid replacement

key messages

‰‰ Evaluation of hydration status, nutritional status, and presence of infection are keys to management of diarrhea ‰‰ Electrolyte and biochemical imbalances are important to be recognized and rectified

24

ch-05.indd 24 19-12-2013 12:08:13 CHAPTER 6

Laboratory Investigations

These are not absolutely essential for effective management of acute diarrhea. In children with watery diarrhea, no fever, and no dehydration, no investigations are required. In children with watery diarrhea with fever and/or with dehydration and in children with mucoid diarrhea, investigations may be needed. • The following investigations may be carried out in order of priority: || Microscopic examination of stools for pus cells, red blood cells and macrophages (cellular exudates), and presence of cysts or vegetative forms of Entamoeba histolytica or Giardia lamblia || Blood investigations, such as pH, base excess, electrolytes, such as N+, K+, hemoglobin level, urea, and osmolality || Record of the pH or reaction of the stools by dipping a strip of pH indicator paper of blue litmus paper in the stools suspension || Culture of stools for enteropathogenic bacteria || Tests for the presence of toxins in the organisms cultured from stools, e.g., distension of the isolated rabbit ileal loop or GM1, enzyme-linked immunosorbent assay (ELISA), etc. || Tests for the presence of rotavirus by electron microscopic examination or by ELISA test.

ch-06.indd 25 18-12-2013 14:32:40 Clinic Consult: Childhood Diarrhea

• Children with frank bloody diarrhea do not require stool examination as the diagnosis of invasive diarrhea is clear. However, if blood does not disappear even after 48 hours of suitable antibiotic therapy, then it may be worth doing a routine examination of stool to rule out an occasional case of acute amebiasis • Stool cultures are practically of no value in the clinical management of children with shigellosis and hence stool cultures are not required. Although only one-third of the cases of dysentery may be caused by Shigella group of organisms, nevertheless the other organisms also need to be treated on the lines of Shigella dysentery. In other cases, isolation of a bacterial organisms or its antibiotics sensitivity has no significance whatsoever in management. Mere isolation of bacterial organisms like Escherichia coli, Klebsiella, etc. does not indicate that it is the responsible pathogen, as they are often cultured from normal stools also. In any case, there is no role of any antibiotic in treatment of these cases. Thus, stool organism or their sensitivity is never the determinant of the choice of antibiotic in a case of diarrhea • In hospitalized infants, appearance of invasive stools denotes either a hospital-acquired gut infection (usually Salmonella typhimurium or a much more severe pseudomembranous colitis, especially in those on broad-spectrum antibiotics). In these cases, sigmoidoscopy may be worthwhile investigation • Whenever systemic infection is suspected on the basis of localizing signs/symptoms and/or persistent pyrexia, appropriate investigations may be done, viz., urine routine, culture, blood culture X-ray, colony stimulating factor (CSF), etc. Examination of peripheral smear for band cells has proved a useful bedside screening test for infants in whom systemic infection is suspected

26

ch-06.indd 26 18-12-2013 14:32:40 Laboratory Investigations

key messages

‰‰ Laboratory investigations are usually not required for diagnosis and management of diarrhea ‰‰ In children with watery diarrhea, with fever and/or dehydration, and in case of mucoid diarrhea or where systemic infection is suspected, investigations may be needed ‰‰ Stool cultures and sensitivities are of no value.

27

ch-06.indd 27 18-12-2013 14:32:40 CHAPTER 7 Management of Acute Diarrhea

Management of acute diarrhea is being discussed in the following headings: • Management of dehydration • Drug therapy in diarrhea • Dietary management.

MANAGEMENT OF DEHYDRATION As per the World Health Organization (WHO) recommendation, the following is the protocol of fluid therapy in dehydration.

Plan A: Prevention of Dehydration • The mother should continue to breastfeed her baby frequently and for longer periods at each feed • A child who is being exclusively breastfed should be given oral rehydration solution (ORS) or plain clean water in addition to breast milk • A child who is not exclusively breastfed may be given ORS solution, soup, rice/dal water, rice kanji, coconut water, barley water, curd/yoghurt, lassi

ch-07.indd 28 18-12-2013 14:34:10 Management of Acute Diarrhea

• The amount of ORS to be given to the baby should be 50–100 mL after each loose stool in a child aged less than 2 years or 100–200 mL in a child aged greater than 2 years • The mother must be taught how to prepare ORS at home. She may also be told that this may be given as frequent small sips from a cup. If the child vomits, the ORS may be repeated after 10 minutes slowly and she should continue to give this until diarrhea stops • Along with the oral rehydration therapy (ORT), the mother should be given instructions to give zinc supplement in the dose of 10 mg in babies less than 6 months and 20 mg in babies above 6 months per day for 10–14 days

Plan B: For Children with Physical Signs of (Some) Dehydration • The child should be given ORS in the first 4 hours at the rate of 75 mL/kg. In case, weight of the baby is not available then the calculation may be done as in table 1 • If after 4 hours the child is still dehydrated, then same amount of ORS may be repeated. The phase of rehydration usually lasts for 6–8 hours

Table 1 Amount of oral rehydration solution to be given during first 4 hours according to age/weight Age Up to 4 months 4–12 months 12 months to 2–5 years 2 years Weight <6 kg 6–10 kg 10–12 kg 12–19 kg Amount 200–400 400–700 700–900 900–1,400

29

ch-07.indd 29 18-12-2013 14:34:10 Clinic Consult: Childhood Diarrhea

• After 4–6 hours, the child should be reassessed for the degree of dehyd­ra­tion and then put on the appropriate plan (A, B, C) for further management • When baby is being sent home from the hospital/clinic, the mother must be educated and instructed regarding preparation and administration of the ORS, continuing feeding at home, danger signs of dehydration and revisit to the hospital in case they are present, provision of normal daily fluid requirements.

Plan C: For Children with Signs of Severe Dehydration • Intravenous (IV) fluids should be started immediately, as any delay can lead to hypovolemic shock. The child should be offered ORS by mouth while the drip is being setup or when the child is able to drink by mouth, even when on IV fluid therapy. The details of the amount and type of IV fluids are described later in this chapter • In situations where IV access fails due to very poor perfusion, one must consider the intraosseous route • Oral rehydration solution via nasogastric route may be used if intraosseous access also fails. Monitoring is very essential during the IV therapy • All such children should be started on ORS ad lib as soon as they are able to drink, even during the course of IV fluid therapy • Once severe dehydration has been taken care of, the child may be shifted to Plan A or Plan B depending upon the degree of dehydration. If the child is still unable to accept well orally and is vomiting or the purge rate is very high (0.5 mL/kg/hour) or has an associated systemic infection, then IV fluids would need to be continued as maintenance therapy (Figure 1).

30

ch-07.indd 30 18-12-2013 14:34:10 Management of Acute Diarrhea

IV, intravenous; ORS, oral rehydration solution.

Figure 1 Treatment algorithm of severe dehydration [World Health Organization (WHO)].

31

ch-07.indd 31 18-12-2013 14:34:10 Clinic Consult: Childhood Diarrhea

ORAL REHYDRATION THERAPY This is done with the help of ORS, sugar-salt solution, food-based solutions, commonly available and culturally acceptable fluids. About 90% of children with diarrhea have no dehydration at the time of their first presentation. Another 8–9% has only mild-to- moderate dehydration. Hence 98–99% of children with simple watery diarrhea can be safely rehydrated with ORS alone or other types of oral rehydration fluids, for example, sugar-salt solution (contains 40 g of sugar and 4 g of salt per liter of water), rice water with salt (contains approximately 55 g of rice and 4 g of salt per liter of water), lassi with salt, coconut water, shikanji (lemonade), soups, thin rice kanji, dal water without salt, and plain water.

Oral Rehydration Solution Glucose electrolyte solution used orally for rehydration and maintenance was initially developed to replace diarrheal fluid losses in cholera and to reduce the need for IV fluids in developing countries. Its scientific basis rests on the fact that glucose linked enhanced sodium absorption in the small intestine remains largely intact during acute diarrhea inspite of mucosal damage or secretory intestinal pathology. Apart from glucose, sodium cotransport occurs with oligosaccharides (maltodextrins), disac­charides (sugar), and starch (rice), as they all release glucose after hydrolysis. Others like amino acids, i.e., glutamine, glycine, and alanine are also known to stimulate sodium absorption. In fact, as these food components are hydrolyzed slowly in the intestinal lumen, they tend to cause lesser osmotic load and hence prove to be more efficient promoters of absorption. If a child is accepting food, then along with it plain water also can be given to prevent the dehydration while maintaining nutrition.

32

ch-07.indd 32 18-12-2013 14:34:10 Management of Acute Diarrhea

Types of Oral Rehydration Solution • World Health Organization (WHO) United Nations International Children’s Fund (UNICEF) ORS • Low osmolarity ORS • ReSoMal for severely malnourished children • Super ORS rice-based maltodextrin, L alanine, L glutamine based. Initially, the WHO and UNICEF formulated a glucose-based oral dehydration solution (G-ORS) to treat and prevent dehydration due to diarrhea of all causes. This remained in vogue for nearly 25 years. Later, however, a WHO task force worked on a reduced osmolarity ORS containing 75 mEq/L sodium and 75 mmol/L glucose (total osmolarity 245 mmol/L) and recommended it as a universal solution for prevention and treatment of diarrheal dehydration to replace the earlier WHO-ORS in all types of diarrheas and at all ages. This recommendation came as a result of studies showing improved efficacy of this ORS in non-cholera diarrhea in infants and children and also with a comparable efficacy in adults with cholera. There was only a marginally elevated risk of asymptomatic hyponatremia. It further carries the programmatic advantage of providing a single formulation for treatment and prevention of all types of diarrheas. A range of acceptable ORS formulations are shown in table 2. The following are the special considerations while treating diarrhea in malnourished children: • High sodium content of the WHO-ORS may lead to fluid and electrolyte disturbances in the child with severe malnutrition, especially in those with edema • Dehydration tends to be overdiagnosed and its severity is overestimated in severely malnourished children • WHO has recommended that the IV route should not be used for rehydration of severely malnourished children, except in cases of shock

33

ch-07.indd 33 18-12-2013 14:34:10 Clinic Consult: Childhood Diarrhea Copper (mmol/L) 45 Zinc (mmol/L) 300 Magnesium (mmol/L) 3 Citrate (mmol/L) 10 10 3 7 – (mmol/L) 80 65 70 70 Cl

+ 20 20 20 40 K (mmol/L)

+ , clorine. – 90 75 60 45 Na (mmol/L) 111 75 60 125 Glucose (mmol/L) , potassium; Cl + , sodium; K + Composition of current and recommended oral rehydration salt solutions Standard WHO-ORS (311 mmol/L) Reduced osmolarity WHO-ORS (245 mmol/L) ESPGAN recommendation ReSoMal for severely malnourished children Composition T ab l e 2 WHO, World Health Organization; ORS, oral rehydration solution; ESPGAN, European Society for Pediatric Gastroenterology and Nutrition; Na

34

ch-07.indd 34 18-12-2013 14:34:10 Management of Acute Diarrhea

• Severely malnourished children have low total body potassium content which may lead to increased mortality. Potassium concentrations of the standard WHO-ORS may be too low to supplement adequately the low potassium levels and also to replace stool losses during diarrhea. Therefore, the WHO recommended a new formulation with sodium concentration of 45 mEq/L and potassium of 40 mEq/L which also provide buffered magnesium, zinc, and copper (ReSoMal), and is recommended by WHO for use in severely malnourished children

Super-oral Rehydration Solution and Rice-based Oral Rehydration Solution Rice powder is predominantly starch (polysaccharide) and some amount of protein. In diarrhea, amylase activity in the intestine is normal. Amylase acts on starch and gradually breaks it down to oligosaccharides and finally to monosaccharide glucose. This process supplies a large number of glucose molecules. However, rather than all these glucose molecules being supplied at one time (as in a standard G-ORS), in rice-based ORS, the polysaccharides are broken down to glucose only gradually. Thus, there is no big osmotic load as may occur with G-ORS. The protein in the rice powder is broken by the proteases into oligopeptides. The oligopeptides are further broken down into peptides and amino acids. As has been pointed out earlier, a sodium amino acid cotransport mechanism also exists, which is similar to the glucose sodium cotransport mechanism. This also increases sodium absorption.

When can Oral Rehydration Therapy Be Stopped? Oral rehydration therapy can be stopped as soon as abnormal losses of diarrheal stool are under control.

35

ch-07.indd 35 18-12-2013 14:34:10 Clinic Consult: Childhood Diarrhea

Oral rehydration therapy should also not be used in following conditions as it is usually unsuccessful in these conditions: • Very high purge rate (>10 mL/kg/hour stool fluid losses) • Persistent vomiting • Severe acidosis/severe dehydration • Convulsions/abdominal distension • Septicemic illness • Glucose-galactose intolerance (rare) • Severe dyselectrolytemia (occasional success stories of ORS, not with ­standing). In these cases, rehydration must be by IV fluids.

Oral Rehydration Therapy in Newborns Diarrhea in newborns may be due to two reasons. One, in which a normal breastfed baby has an increased frequency (normal increased frequency), and the other, in which it is due to a systemic bacterial illness like septicemia, meningitis, etc. Use of ORT in both these conditions is not indicated. In the first instance, it is not required (and may lead to sodium and water retention), and in the second instance, immediate hospitalization and management with IV fluids and antibiotics is what is actually needed. Delay in hospitalization, because of the temptation to use ORT at home, can be dangerous in this situation.

Some Practical Aspect of Oral Rehydration Therapy Nonacceptance or refusal to take ORS is a very common problem. This may be because the child is not really dehydrated. However, if the child is dehydrated but not accepting ORS then it must be assessed for a systemic infection and given IV antibiotics.

36

ch-07.indd 36 18-12-2013 14:34:11 Management of Acute Diarrhea

Vomitings are also frequently associated in children with diarrhea, and because of this, the child may not be able to accept ORS. Vomits are more likely to occur if the child is allowed to take gulps of ORS from a glass/cup. Small sips given frequently are usually well retained and these should be offered in cases of vomiting. There is no need of boiling water for making ORS or boiling it after mixing ORS. If a fridge is available then a prepared solution can be kept up to 12 hours.

INTRAVENOUS REHYDRATION This is done by use of the following IV fluids (Table 3): • Ringer’s lactate/Ringer’s lactate with 5% dextrose (most preferred) • Normal saline (0.9% NaCl) • N/2 saline—replacement of stool losses.

Table 3 Composition of intravenous solutions Fluid Sodium Chlorine Potassium Calcium Lactate (Na+) (Cl–) (K+) (Ca2+) Normal saline 154 154 – – – (0.9% NaCl) Half normal saline 77 77 – – – (0.45% NaCl) One-fourth normal 38.5 38.5 – – – saline (0.225% NaCl) Ringer’s lactate 130 109 4 3 28 Electrolyte 26 22 19 – – phosphorous

37

ch-07.indd 37 18-12-2013 14:34:11 Clinic Consult: Childhood Diarrhea

EMERGENCY REPLACEMENT IN HYPOVOLEMIC SHOCK This is done by giving the IV fluids as in table 4. The child should be reassessed every 15–30 minutes. If hydration status is not improving then the child may be given IV drip more rapidly. Also, the child should continue to get ORS (5 mL/kg/hour) as soon as the child can drink. The child should be assessed after 3 hours and in infant after 6 hours. Dehydration may be classified afresh and the appropriate plan (A, B, or C) should be continued.

INTRAOSSEOUS INFUSION In an emergency where due to shock the veins are collapsed and not accessible, intraosseous infusion will need to be given into the bone marrow. The preferred site is the proximal tibia as shown in figure 2. A needle of 15–18 gauge (or if not available even a 21 gauge needle or any large bore needle) is used. The needle is inserted at 90° angle with the bevel pointing toward the foot and pushed gently but firmly with drilling or twisting motion. It is stopped being pushed when there is a sudden decrease in resistance or

Table 4 Protocol of giving intravenous (IV) fluids in hypovolemic shock Age First 30 mL/kg Then 70 mL/kg <12 months Over 1 hour* Next 5 hours >12 months Over 30 minutes* Next 2½ hours *Repeat again, if pulse is weak or still not detectable.

38

ch-07.indd 38 18-12-2013 14:34:11 Management of Acute Diarrhea

Figure 2 Intraosseous infusion—infusion needle placed in the anterior surface of the leg at the junction of the upper and middle third of the tibia. Source: World Health Organization. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Illnesses with Limited Resources, illustrated edition. Mumbai, India: Medica Press International; 2005. pp. 122-30.

blood is aspirated by a 5 mL syringe. Using another 5 mL syringe prefilled with normal saline, 3 mL of this fluid is injected slowly to confirm that there is no leakage or infiltration. The needle is then secured into position and IV fluid is given through the infusion equipment. The intraosseous infusion should be stopped as soon as the venous access is available and should not continue for more

39

ch-07.indd 39 18-12-2013 14:34:11 Clinic Consult: Childhood Diarrhea

than 8 hours. Complications include incomplete penetration of the bony cortex (infiltration occurs under the skin), penetration of the posterior bone cortex (calf becomes tense), and infection (local cellulitis).

MAINTENANCE THERAPY BY INTRAVENOUS FLUIDS This would be needed if the child has vomiting and unable to accept well orally or the purge rate is very high or has systemic infections. The amount of maintenance fluid needed is as in tables 5 and 6.

Maintenance Electrolytes • Sodium: 2–3 mEq/kg/24 hour • Potassium: 1–2 mEq/kg/24 hour.

Table 5 Body weight method for calculating maintenance fluid volume Body weight Fluid per day 0–10 kg 100 mL/kg 11–20 kg 1,000 mL + 50 mL >20 kg 1,500 mL +20 mL/kg for each kg >20 kg

Table 6 Maintenance fluid requirements based on age Age mL/kg/2 hour Age mL/kg 24 hour 10 days to 3 months 150 1–3 years 100 3–6 months 130 3–7 years 80 6 months to 1 year 120 >7 years 60

40

ch-07.indd 40 18-12-2013 14:34:11 Management of Acute Diarrhea

Calculating Rate of Infusion The IV Fluids need to be given accurately and this can be monitored. If a syringe pump is available, then this monitoring is done digitally. Otherwise, this can be done by counting the drops per minute. The calculation is as per the formula given below: Total volume to be given in mL = Rate in mL/hour. Duration in hours As the microtipped IV set is designed to provide 60 drops in 1 mL, the rate in mL/hours equals the drops per minute. An example of this is that if 480 mL of IV Fluid is required in 24 hours then the rate of infusion will be: Total volume to be given in mL 480 mL ==20 mL/hour. Duration in hours 24 hours

key messages

‰‰ Breastfeeding should be continued to prevent dehydration ‰‰ Babies not exclusively breastfed should be given oral rehydration fluids ‰‰ Zinc supplements should be given along with oral rehydration ‰‰ In severe dehydration, parenteral fluids should be started based on body weight or age ‰‰ Ringer’s lactate/Ringer’s lactate with 5% dextrose is the fluid of choice for parenteral rehydration.

41

ch-07.indd 41 18-12-2013 14:34:11 CHAPTER 8 Drug Therapy in Diarrhea

It needs to be emphasized that diarrhea-like fever is only a symptom and not a disease per se. It can be caused by a number of factors and by different pathogenetic mechanisms. It is important to identify the underlying cause and to treat the same rather than to take action for stopping the symptom of diarrhea. In majority of cases, acute diarrhea is a self-limiting illness warranting nothing more than fluids. Majority of children with acute diarrhea have neither cholera nor associated systemic infection and do not require any drugs. The major problem in children with watery diarrhea is loss of fluids and electrolytes and consequent dehydration. This loss whether due to mucosal damage [rotavirus, enteropathogenic Escherichia coli (EPEC)] or due to stimulation of secretory mechanisms which occurs as with enterotoxigenic E. coli (ETEC), and Vibrio cholera is entirely self-limiting in settling down within 3–5 days. Fever and coryza are also often present in rotavirus infection and even in ETEC diarrhea and hence, by themselves, do not constitute indications for the use of antibiotics. One may also understand this when one realizes that even with bacterial diarrhea due to ETEC, the cause of diarrhea is due to action of toxins released by the bacteria rather than by the bacteria themselves which remain only on superficial layers of mucosa and are not invasive in character causing no structural damage to the intestine. Even in cases of cholera the antibiotics are

ch-08.indd 42 18-12-2013 14:34:32 Drug Therapy in Diarrhea

given to prevent the occurrence of secondary cases as the course of disease is totally unaffected by the antibiotics in the patient himself. Therefore, the only rational treatment for watery diarrhea in infants and children is replacement of fluids and electrolytes and for this oral rehydration solution is the best and probably the only treatment needed. Mucoid diarrhea cases are largely caused by the same organisms as watery diarrhea. Therefore, the approach in these cases is on similar lines. Occasionally, invasive diarrhea may start as mucoid diarrhea, but very soon, the stools start having blood in these cases. This would become apparent within a few hours.

ANTIMICROBIAL THERAPY As pointed out above, most episodes are caused by pathogens for which antibiotics are not needed or effective. Routine empirical use of antibiotics for infectious diarrhea should be avoided because of the self-limited nature of most cases. For patients with severe invasive or prolonged diarrhea or who are at high risk of complications, empirical treatment with a relevant antibiotic is useful. The following are the specific indications for antimicrobial therapy in acute/persistent diarrhea: • Dysentery (presence of gross blood and pus in stools): In all probability, shigellosis. Presence of few white blood cell (WBC) and red blood cell (RBC) in stool does not indicate invasive infection. Only sheets of pus cells on routine stool examination are indicative of shigellosis and merits antibiotics. Further, Shigella group of organisms are responsible for nearly one-third of the cases of dysentery. Yet, all other causative organisms need to be treated on the same lines

43

ch-08.indd 43 18-12-2013 14:34:32 Clinic Consult: Childhood Diarrhea

• Suspected cholera • Associated extraintestinal systemic infections like pneumonia, septicemia, meningitis, and urinary tract infection (UTI) causing parenteral diarrhea • Severe malnutrition or immunocompromised child • Giardiasis: More common than amebiasis in children • Amebiasis: Less common in children, more in adults.

Antimicrobial Agents Used to Treat Bloody Diarrhea If possible, the choice of antibiotics should be based on recent susceptibility data from Shigella strains isolated in the area. If information on local strains is not available, data from nearby areas or from recent regional epidemics should be used. Although only one-third of cases of dysentery may be caused by Shigella group of organism, it is not possible to distinguish other cases either clinically or even by routine investigations and they are also treated on the same line as of Shigella dysentery. Therefore, irrespective of the causative organism, the choice of antibiotic is the same. • Ampicillin, cotrimoxazole: No longer recommended due to emerging resistance • Nalidixic acid: It has been the drug of choice for the last several years but over the last decade, nalidixic acid-resistant Shigella dysenteriae type 1 has been reported from several regions of South and Middle-east Asia, Eastern and Southern Africa. In addition, there has been a recent outbreak of nalidixic acid- resistant Shigella sonnei from Israel. Widespread use of nalidixic acid may reduce the efficacy of ciprofloxacin as nalidixic acid- resistant Shigella strains are reported to show some degree of cross-resistance to ciprofloxacin. Further, the cost of treatment with nalidixic acid is about three times that of ciprofloxacin

44

ch-08.indd 44 18-12-2013 14:34:32 Drug Therapy in Diarrhea

• Fluoroquinolones: || Ciprofloxacin: World Health Organization (WHO) recom­ mends ciprofloxacin, as the drug of choice for all patients with bloody diarrhea, irrespective of age (Table 1) || Norfloxacin: It has been found to significantly reduce the duration of diarrhea and presence of blood in stools in children when compared to nalidixic acid. No joint problem was encountered in a study at up to 4 months follow-up. Single dose of norfloxacin in adults has also been found to be effective || Ofloxacin: It has been compared to nalidixic and (55 mg/kg/ day for 5 days) in a randomized controlled trial (RCT) and shows significantly lesser proportion of treatment failures || The fluoroquinolones are not approved for children in India by Drugs Controller General (India) (DGCI). Also Shigella is currently showing increasing resistance to the fluoroquino­ lones, necessitating the use of alternative antibiotics

Table 1 Antimicrobials for treatment of bloody diarrhea Antimicrobial Dose Duration First line 1. Ciprofloxacin 15 mg/kg twice a day 3 days 2. Norfloxacin 20 mg/kg/day 5 days 3. Ofloxacin 15 mg/kg/day 5 days Second line 1. Cefixime 8 mg/kg/day 5 days 2. Azithromycin 6–20 mg/kg/1–1.5 g 1–5 days (once a day orally) 3. Ceftriaxone 50–100 mg/kg once 2 days (once a day intramuscularly) 4. Pivmecillinam 20 g/kg/1–1.5 g 5 days

45

ch-08.indd 45 18-12-2013 14:34:32 Clinic Consult: Childhood Diarrhea

• Alternative therapy options: Cefixime, ceftriaxone, azithromycin, newer quino­lones, and pivmecillinam are usually effective for treatment of multiresistant strains of Shigella in all age groups. || Cefixime: Has significantly higher clinical and bacteriological cure rates || Ceftriaxone: Injectable route, limited efficacy data || Azithromycin: Rapid development of resistance, limits their wide­spread use || Pivmecillinam: Higher cost and no pediatric formulation for pivme­cil­linam. It is recommended that these second-line drugs should be used only when local strains of Shigella are known to be resistant to ciprofloxacin.

Antibiotics Not Effective Against Shigella Some antibiotics are very commonly used in diarrheas. They are not effective against Shigella and have no role in case of any diarrheas (Table 2). The most common of these antibiotics used is amikacin. Shigella may show in vitro sensitivity to amikacin. But, it is an intracellular organism where amikacin does not reach due to its poor cellular penetration in gut mucosa.

Table 2 Antimicrobials not effective against Shigella yy Ampicillin, amoxicillin, chloramphenicol, cotrimoxazole, tetracycline yy Furazolidone, nitrofurans yy Aminoglycosides, including amikacin yy First- and second-generation cephalosporins yy Colistin yy Nalidixic acid

46

ch-08.indd 46 18-12-2013 14:34:32 Drug Therapy in Diarrhea

How to Assess Response to Therapy? It is important to note that diarrhea takes 2–3 days to cease after disappearance of blood. If there is minimal or no improvement after 2 days, resistance to the initial antimicrobial is assumed and it should be stopped. Improvement is assessed by fall in fever, less blood in stool, decreased abdominal pain. A second antimicrobial; for example, ceftriaxone in the dose of 50–100 mg/kg once (intramuscularly) or twice (intravenously) a day or cefixime (8 mg/ kg/day 12 hourly) should be given for 2–5 days. Risk factors for death are greatest among infants, nonbreastfed, dehydrated, or malnourished children. History of convulsions or measles and presence of unconsciousness, hypo- or hyperthermia at first contact are indicators of severe illness, and these children are at greater risk of dying. Such children should be referred to the hospital for treatment. Those with severe malnutrition should be additionally screened and treated for associated sepsis.

Treatment of Other Agents Causing Bloody Diarrhea • Campylobacter jejuni, Schistosoma, Salmonella, enteroinvasive, and enterohemorrhagic Escherichia coli: All these pathogens require special laboratory procedures for isolation. Infection with Campylobacter jejuni responds to early treatment with an effective antimicrobial, e.g., erythromycin, but most episodes recover by the time the laboratory diagnosis is made. Antimicrobial therapy in Salmonella infection may prolong the carriage of the pathogen • Clostridium difficile colitis: Infection with C. difficile (due to toxin A and B), though uncommon, may be considered in children on prolonged antimicrobial therapy and hospitalization

47

ch-08.indd 47 18-12-2013 14:34:32 Clinic Consult: Childhood Diarrhea

While use of nearly any antibiotic may result in C. difficile toxin production, beta-lactam antibiotics (e.g., cephalosporins and penicillins) and clindamycin are most commonly implicated. Clinical symptoms range from mild to severe consisting of bloody diarrhea, abdominal cramps and fever • Treatment: Almost 25% of the patients respond to discontinuation of the offending antibiotic • When the initial symptoms persist even after the offending anti­ biotic has been discontinued or those with moderate to severe disease, treatment with metronidazole (oral or intravenous) should be given • Vancomycin (orally) should be reserved for second-line therapy to prevent or minimize development of vancomycin-resistant bacterial pathogens (i.e., Enterococcus and Staphylococcus aureus). • Relapses of infection are seen in up to 33% and should be treated as initial therapy with metronidazole as the preferred drug • Nongastrointestinal infection, e.g., pneumonia, septicemia, meningitis, urinary tract infection associated with bloody diarrhea: All children, particularly infants less than 3 months of age or those severely malnourished, should be carefully screened for nongastrointestinal infection, e.g., pneumonia, septicemia, meningitis, and UTI. Early detection and appropriate treatment of associated systemic infection in malnourished children can reduce the mortality significantly. Specific therapy for associated nondiarrheal acute infection is as for other children.

Treatment of Cholera The mainstay of therapy for cholera is rehydration with oral rehydration solution (for some dehydration) or intravenous Ringer’s lactate (for severe dehydration).

48

ch-08.indd 48 18-12-2013 14:34:32 Drug Therapy in Diarrhea

Antimicrobials may be used as an adjunct to oral rehydration therapy (ORT) for severely purging cholera patients to reduce the rate of stool output, minimize fluid requirement, and stop excretion of Vibrio cholera in the stool. • Tetracycline (12.5 mg/kg four times a day for a period of 3 days) • Erythromycin (12.5 mg/kg given four times a day for 3 days) • Cotrimoxazole (trimethoprim 5 mg/kg or sulfamethoxazole 25 mg/kg twice a day for 3 days) • Furazolidone (1.25 mg/kg four times a day for 3 days) • Doxycycline (6 mg/kg or 300 mg in adults given as a single dose) has been found to be as effective as multiple doses of tetracycline in treatment of cholera. In children less than 8 years of age, tetracyclines have been found to cause discoloration of teeth and delay in bone growth and hence alternative therapy is preferred.

Treatment of Amebiasis Young children should not be routinely treated for amebiasis, as it is an infrequent cause of bloody diarrhea in children. Only 2% of acute dysentery cases are because of amebiasis. The incidence increases with age and most episodes are in adults. Amebiasis should be considered only if two different antibiotics usually effective for Shigella in the area have been given sequentially without showing signs of clinical improvement, or if a microscopic examination of fresh stool done in a reliable laboratory shows trophozoites of Entamoeba histolytica containing RBC. Treatment is with metronidazole—10 mg/kg three times a day for 5–10 days. This causes severe anorexia and even vomiting. Therefore, it must be given only if there is an actual indication and not as a combination with other antibiotics, which is a very common practice. Supportive care is very essential while treating dysentery, i.e., treatment of dehydration and control of associated fever.

49

ch-08.indd 49 18-12-2013 14:34:32 Clinic Consult: Childhood Diarrhea

Treatment of Giardiasis Treatment is indicated only if Giardia trophozoites are identified in stool or duodenal fluid. Agents to treat giardiasis are metronidazole (5 mg/kg given three times a day for 5 days), tinidazole (as a single dose 50 mg/kg orally; up to a maximum of two doses), albendazole, and mebendazole (equally effective and better tolerated than metronidazole). Nitazoxanide (nitrothiazolyl-salicylamide derivative, dose 12– 47 months 100 mg 12 hourly for 3 days; 4–11 years 200 mg 12 hourly for 3 days) significantly better in achieving earlier recovery from diarrhea. There is presently limited evidence from randomized controlled trials to recommend routine treatment with nitazoxanide for giardiasis. Additionally, the cost of treatment with nitazoxanide is almost seven times higher than that with metronidazole.

Combination Therapy Several combinations of antibacterial agents and of antibacterials with antidiarrheals are available. They offer no extraclinical benefit as compared to a properly selected single antibacterial agent for the small proportion of diarrheal illness where indication for their use exists. Combination therapy can promote overgrowth of harmful resistant bacteria and the antimotility agents that are often a part of these combinations may delay excretion of invasive pathogens.

OTHER DRUGS

Alteration of Intestinal Motility Antimotility drugs like loperamide have been used to decrease the frequency of stools. But they have no effect on the basic pathogenic mechanism, i.e., excess fluid and electrolyte losses which continue

50

ch-08.indd 50 18-12-2013 14:34:32 Drug Therapy in Diarrhea

despite apparent decrease in frequency. They may produce a false sense of well-being. They decrease intestinal peristalsis and delay elimination of causative organisms. In fact, as stimulated intestinal motility is an essential host defense mechanism to overcome diarrheal illness, the use of antimotility agents cannot be justified at all. In infants, they can cause paralytic ileus, abdominal distension, respiratory depression, bacterial overgrowth, and sepsis. These drugs potentiate Shigella infection and produce toxic colon. These severe side effects far outweigh their limited benefits in reducing stools frequency. Hence they should not be used. Opiates and opiate-like antispasmodic combinations (tincture of opium, camphorated tincture of opium or paregoric, codeine, dipheno­xylate with atropine)—these motility suppressants are contraindicated in children because of their potentially severe side effects.

Alteration of Secretion The antisecretory properties of the new synthetic enkephalinase inhibitor, racecadotril (aceptorphan), are attributed to activa­tion of endogenous enkephalins, secreted by myenteric and submucous plexus in the digestive tract. It enhances the antisecretory role of the neurotransmitter, enkephalin. This compound differs from i-opiate receptor agonists like loperamide and diphenoxylate in the way that its antisecretory mechanisms do not effect intestinal motility. This drug has been evaluated in a small number of children and adults with diarrhea in randomized controlled trials with varying results. More evidence of its efficacy and safety from well-designed randomized controlled studies done in our settings is needed.

51

ch-08.indd 51 18-12-2013 14:34:32 Clinic Consult: Childhood Diarrhea

Adsorption of Toxins or Fluid Kaolin, pectin, fiber, bismuth subcarbonate, and activated charcoal were once very popular. There is no conclusive evidence that they reduce stool losses, duration of diarrhea, or stool frequency. Moreover, their use diverts the attention from the more important factor, i.e., management of dehydration.

Alteration of Intestinal Microflora Prebiotics are nondigestible food ingredients (e.g., inulin, oligosac­ charides), which selectively stimulate the growth and/or activity of one or limited number of beneficial bacteria in the colon. Probiotics are products with a sufficient number of viable microorganisms to alter the host’s microflora which allows a beneficial healthy ecology to prevail in the intestine. An effective probiotic agent is one which will provide sufficient microorganisms that can survive the host’s digestive process, colonize the gut, and produce a beneficial response in the host without pathogenic or toxic adverse effects. Examples are Saccharomyces boulardii, Lactobacilli, Bifidobacteria, and Streptococcus thermophilus. Early administration of these probiotics along with ORS is claimed to decrease the amount and duration of diarrhea. Yoghurt/ curds are rich sources of Lactobacilli.

Zinc Deficiency Zinc deficiency has been found to be widespread among children in developing countries and occurs in most of Latin America, Africa, the middle East, and South Asia. Zinc has been identified to play a critical role in metallo­ enzymes, polyribosomes, the cell membrane, and cellular function.

52

ch-08.indd 52 18-12-2013 14:34:32 Drug Therapy in Diarrhea

It also plays a central role in cellular growth and in the function of the immune system. Its loss in diarrhea compromises cellular health and immunity. Daily dose of 20 mg of zinc as (zinc sulfate or zinc acetate or zinc gluconate) once daily for 10–14 days (10 mg/day for infants below 6 months) is recommended in children up to 5 years.

key messages

‰‰ Routine empirical use of antibiotics for infectious diarrhea should be avoided ‰‰ Specific indications for antimicrobials are dysentery, suspected cholera, associated systemic infections, severely malnourished, or immunocompromised and in cases of giardia or ameba infestation ‰‰ Fluoroquinolones and cefixime have replaced nalidixic acid as the first choice for dysentery ‰‰ Zinc supplementation and probiotics have been shown to be beneficial in acute diarrhea.

53

ch-08.indd 53 18-12-2013 14:34:32 CHAPTER 9

Dietary Management

Dietary management is a subject often missed in crowded outpatients. It is as important as rehydration and certainly more important than the drugs. Homemade oral rehydration solution (ORS) like shikanji, lassi, chacch, rice-based ORS, panna, are always to be encouraged, as recommended in the previous chapter. The most important thing that needs to be emphasized is that food should not be withheld during diarrhea. This is essential for the gut nutrition and the nutrition of the child. Breastfeeding should be continued. Breastfed children are less prone to diarrhea. Breast milk contains viable phagocytes and other protective substances, such as secretory immunoglobulin A (IgA) and specific IgM which protect against most enteropathogens but possibly not against rotavirus infection. Also, Lactobacillus bifidus also has protective value. If the child is on top milk, it should not be diluted, except in the very rare cases where temporary lactose intolerance is suspected. Nonlactose milk (soya milk) is also being overprescribed because of the fear of lactose intolerance without this being substantiated (low pH of stools, i.e., less than 5.5 on two occasions). Also, there is soya milk cross allergy in nearly 30% cases of cow’s milk protein allergy.

ch-09.indd 54 18-12-2013 14:34:58 Dietary Management

The food should be soft and easily digestible. It should be given as small frequent feeds which are well tolerated. For infants, this may include khichdi, dalia, mashed bananas, mashed rice and dal, biscuits, etc. (Figure 1). For older children, it may be the usual solid food that he was having prior to illness. Along with this usual diet of the child, plenty of plain water should be given.

Figure 1 Food during diarrhea.

55

ch-09.indd 55 18-12-2013 14:34:58 Clinic Consult: Childhood Diarrhea

Giving yoghurt, curd, and kheer will be of an additional advantage to these children, especially those having lactose intolerance. Soft drinks and fruit juices with high sugar content should preferably be avoided during diarrhea. Contrary to popular belief, most children tolerate small quantities of fats and oils which are rich sources of energy, and the diarrhea does not get worse.

key messages

‰‰ Homemade ORS like shikanji, lassi, chacch, panna, and rice-based ORS should be encouraged ‰‰ Breastfeeding should be continued wherever possible ‰‰ Feeding should be continued and food should be soft and easily digestible ‰‰ Fats are well tolerated and should be given in small quantities.

56

ch-09.indd 56 18-12-2013 14:34:58 CHAPTER 10 Persistent/Protracted/Recurrent/ Chronic Diarrhea

In about 5% of acute diarrhea cases in the community, illness may last for more than 2 weeks or 3 weeks, because of persistent colonization of upper small intestines by microbes, dietary allergies (especially in very young infants), and carbohydrate intolerance (because of intestinal damage resulting in low levels of disaccharidases). Infants and children with decreased host immunity, such as after an attack of measles, or delayed repair of intestinal damage because of associated protein–energy malnutrition (PEM) are more prone to protracted diarrhea. Younger infants who are weaned very early develop intolerance to food proteins such as cow’s milk or even soya milk. Poor personal hygiene and environmental or food contamination may lead to recurrent intestinal infections before the infant recovers from a previous episode. Protozoal infections with Giardia lamblia or Entamoeba histolytica and inadequate treatment of acute diarrhea are other important causes. Epidemiologically, around 10% of all acute diarrheal episodes tend to persist beyond 14 days. However, majority of these episodes represent only a normal variation in natural history of different etiological agents. A study has shown that 10% of even rotavirus diarrhea may last for as long as 21 days but may have no other clinical problems. The frequency and consistency of stools following

ch-10.indd 57 18-12-2013 14:35:25 Clinic Consult: Childhood Diarrhea

Shigella infection very often last for several days following acute illness. Hence, mere prolongation of diarrheal episode should not become a cause of worry. Attempt should be made to focus on those episodes, which are associated with weight loss, as these are the cases, which are likely to have a bad outcome. In these children, attention should be focused on adequate nutrition intake and selective judicious use of antimicrobials. Low lactose diets may help when there is carbohydrate intolerance. If the child is given half-diluted milk for a few days with a phased increase in the concentration of milk given in the next week, most cases of protracted diarrhea improve. Prevention and management of protracted diarrhea primarily involves encouragement of breastfeeding and good nutritional management of acute diarrhea.

PERSISTENT DIARRHEA This has been defined by World Health Organization (WHO) as a diarrhea starting acutely and lasting for more than 14 days. This is seen largely in infants, with more than 60% of episodes occurring within 6 months of age and 90% before 1 year of age. About 10% of acute diarrheal episodes tend to become persistent. The term “protracted” means a drawn out prolongation of illness. However, for practical purposes, persistent diarrhea episodes, which are associated with failure to thrive, have been labeled as protracted diarrhea. About 10% of persistent diarrhea cases develop the problem of weight loss or inadequate weight gain. The exact cause of persistent/protracted diarrhea is not known. A variety of risk factors have been thought of. These include malnutrition, younger age group, impaired cell-mediated immunity, recent introduction of animal milk, enteroadherent Escherichia coli, enteropathogenic E. coli (EPEC), Shigella and inappropriate use of

58

ch-10.indd 58 18-12-2013 14:35:25 Persistent/Protracted/Recurrent/Chronic Diarrhea

antibiotics. It is also thought that the early introduction of top milk introduces them to pathogenic bacteria as well as foreign protein, which causes occurrence of recurrent gut infection and sensitization of the infants to the foreign proteins. Malnutrition leads to delay in replenishment of damaged gut mucosa causing an increased duration of diarrhea. Apart from the possible role of enteropathogens, a large number of specific conditions may be responsible for causation of persistent diarrhea. Majority of these cases have some underlying factors: systemic infections, persistent gut infection, lactose intolerance, cow’s milk protein intolerance (CMPI), mucosal damage, malnutrition (PEM/vitamin A/zinc deficiency), and colitis/antibiotic colitis.

Systemic infection: These infections tend to be recurring and children need to be carefully screened to detect and manage these infections. This means complete blood count, urine examination and culture, X-ray of chest, Mantoux, and blood culture. In areas where human immunodeficiency virus (HIV) is highly prevalent, relevant investigations should be carried out.

Persistent gut infection: Salmonella typhimurium is an important enteropathogen in persistent diarrhea. Enteroadhesive and entero­ aggregative Escherichia coli are the two other important causes. Lactose intolerance: It is due to lactase enzyme which is present in the most superficial layers of jejunal mucosa and hence most vulnerable to damage. Lactose intolerance appearing after 5–7 days of diarrheal episode warrants active management. Suggestive clinical history of watery, explosive, frequent tools with red perianal area and buttocks coupled with demonstration of reducing substances and a reduced pH of less than 5.5 in freshly passed stools, i.e., within 15–30 minutes is usually enough to establish diagnosis of lactose intolerance.

59

ch-10.indd 59 18-12-2013 14:35:25 Clinic Consult: Childhood Diarrhea

Cow’s milk protein intolerance: It presents clinically just like lactose intolerance, although more difficult to diagnose and both may coexist. A useful pointer to distinguish between the two is that while in milk protein intolerance, the child gets diarrhea even on small amount of milk of milk products; in lactose intolerance, the child is able to tolerate reduced amount of milk, especially in milk-based diets. If a child on reduced milk content does not respond, then it is advisable to completely withdraw the milk and milk products.

Mucosal damage: This damage leads to multiple absorptive defects leading to persistence of diarrhea and worsening of nutritional status. It also leads to hypersensitivity to cow’s milk as the ingested milk proteins cause an immune-mediated injury.

Colitis: This is seen in quite a large number of cases and some of these may also be because of unwarranted use of antibiotics (antibiotic colitis).

Malnutrition: While malnutrition prolongs the duration of diarrhea, diarrheal illness itself helps to worsen the nutritional status and thus sets in vicious malnutrition–diarrhea–malnutrition cycle. These children also have multiple vitamin and mineral deficiencies, especially of zinc. It is because of this reason that addition of zinc in therapeutic regimes has helped in the management and prevention of diarrhea. Occasionally, one might see persistent/chronic diarrhea in early infancy in breastfed babies due to what is known as “allergic proctocolitis”. These babies may be allergic to cow’s milk protein, which may be getting passed on to them through the breast milk of their mother, who is consuming cow’s milk and which may be even in the form of milk in tea. The condition gets further aggravated by multiple courses of antibiotics, which concomitantly causes

60

ch-10.indd 60 18-12-2013 14:35:25 Persistent/Protracted/Recurrent/Chronic Diarrhea

vitamin K deficiency. In these babies excluding cow’s milk in all forms in the mother’s died leads to relief.

RECURRENT DIARRHEA Some children between 6 months to 5 years of age suffer from recurrent but distinct episodes of acute diarrhea. It is defined as occurrence of six or more episodes per year or more than three episodes in 6 months or more than two episodes in 3 months. Most of the cases are because of poor environmental conditions of these patients and their malnutrition because of which they tend to fall sick repeatedly. Each of these recurrent episodes may need to be dealt with as a fresh episode of acute diarrhea. Yet another entity is the “Toddlers diarrhea” seen in children of affluent families. These children have frequent stools which become watery by the evening. Fluid diet (milk, fruit juices) seems to aggravate the problem. Putting them on semisolid/solid diet containing some fiber helps. Withdrawing fruit juices, in particular, is quite beneficial.

CHRONIC DIARRHEA In this condition, the onset of diarrhea is more insidious and usually less watery in nature. The stools are about four to five times per day and usually semisolid. This type of condition is seen more often in children above 3 years of age. Occasionally, the stools may be bulky (even fatty and foul smelling) and in some cases may seem to suggest malabsorption. The condition of chronic diarrheas is rare. In India, giardiases and tropical enteropathy (due to deprived environmental conditions) have often been seen as the most common causes, although they are more likely to present as recurrent or persistent diarrheas. Now

61

ch-10.indd 61 18-12-2013 14:35:25 Clinic Consult: Childhood Diarrhea

reports from different parts of the country indicate higher incidence of celiac disease. In children aged 6 months to 2 years, the common causes may be giardiasis, cow’s milk allergy, celiac disease. In children above 2 years, the causes may be celiac disease, irritable bowel syndrome, functional causes, and lactose intolerance. Pancreatic insufficiency and cystic diseases are also no longer infrequent causes.

Management Parents get quite worried when the diarrhea persists beyond 3–5 days and pester the physician for action. As stated above, even in natural history of acute diarrhea, many episodes may last beyond 7 days and hence would not require management on the lines of persistent diarrhea. Persistent diarrheal episodes, especially those associated with failure to thrive, are the ones which will cause worry to the treating doctor. The difficulty in managing these children arises from the fact that in most cases of persistent diarrhea, a single etiological factor may not be responsible for the particular episode. In fact in majority of the episodes, multiple factors may be operative. Moreover, most of these children are quite moribund requiring urgent therapeutic intervention, even while the diagnostic workup is underway.

Domiciliary Management It is important to maintain nutritional and hydration status during this period and to avoid drugs (unless absolutely warranted) during this stage. Some children may have clinical and laboratory evidence of lactose intolerance even at such an early stage of diarrheal disease, but as pointed out above, this usually warrants no energetic management. Unless red alert signals are present, these children can be managed at home. Foods like curd, banana, mashed potatoes,

62

ch-10.indd 62 18-12-2013 14:35:25 Persistent/Protracted/Recurrent/Chronic Diarrhea

khichdi, dalia, etc. should be given in large amounts to meet the increased caloric demands during this time together with continued breastfeeding. Low lactose foods like milk-based cereal diets (suji ki kheer, dudh ka dalia, etc.) can help to decrease the lactose load while continuing to provide adequate calories. Addition of oils in the cereal diet can increase the calorie density of food and help in maintaining nutritional balance. Top milk may be required to be restricted (30–50 mL/kg/day) but should not be replaced by soya milk preparation at this age. In fact, the incidence of soya protein intolerance following acute diarrhea is almost 15 times more than that of CMPI. Hence, in no case should soya milk be introduced in the diet of a child with diarrheal episode of less than 14 days duration.

Multivitamins and Minerals Supplement All children with persistent diarrhea should receive daily supple­ mentary multivitamins and minerals for 2 weeks. These supplements should be given in the dose of two recommended dietary allowances (RDAs) every day. For example, a 1-year-old child should be given folate 50 mg, zinc 10 mg, vitamin A 400 mg, iron 10 mg, copper 1 mg and magnesium 80 mg.

Hospital Management Any child, who presents with a prolonged diarrheal episode along with weight loss, should be hospitalized. These children can have an unpredictable course and may become serious at any time. Moreover, they would require repeated investigations, which may not be possible in an outpatient situation. After admission, a detailed history should be taken regarding the onset, duration, character of stools at the onset, and any subsequent change, associated features like anorexia, fever, cough, urine

63

ch-10.indd 63 18-12-2013 14:35:25 Clinic Consult: Childhood Diarrhea

frequency, etc. and the management received (drugs, diet, etc.) till then. Physical examination of the child should include assessment of nutritional and hydration status and careful screening for any associated infections [chronic suppurative otitis media (CSOM), pneumonia, and even meningitis]. Preliminary investigations should include stool examination for pus cells, ova, cysts, and red cells and for pH and reducing substances. A total and differential leukocyte counts, including band counts and blood culture should also be obtained. A urine examination and culture (if required) and an X-ray of chest should be obtained in all cases. Stool cultures have little value as organisms grown in routine culture of stool may not necessarily be enteropathogens and hence their antibiotic sensitivity also has no implication in choosing antibiotics. If available, stool osmolality and electrolytes may be obtained. A stool osmotic gap (total osmolarity = 2 × sodium content) of less than 50 is suggestive of secretory diarrhea, which may require treatment for sepsis and prolonged parenteral nutrition The stepwise investigation protocol is as suggested below:

Phase I: Clinical history, including specific amounts of fluids ingested per day, physical examination, including nutritional assessment, stool examination (pH reducing substances, smear for white blood cell count, fat, ova, and parasites), stool cultures, stool for Clostridium difficile toxin, and blood studies (complete blood cell count, erythrocyte sedimentation rate, electrolytes, blood urea nitrogen, creatinine). In areas where HIV is highly prevalent, appropriate investigations, including stool examination for isospora should also be carried out.

Phase II: Sweat chloride 72-hour stool collection for fat determination of stool for phenolphthalein, magnesium sulfates, phosphate, and

hydrogen (H2) breath tests.

64

ch-10.indd 64 18-12-2013 14:35:25 Persistent/Protracted/Recurrent/Chronic Diarrhea

Phase III: Endoscopic studies, small bowel biopsy, sigmoidoscopy, or colonoscopy with biopsies and barium studies. In large majority of cases of protracted diarrhea, no single etiological diagnosis is possible. These children are often moribund with fluid, electrolyte, and nutritional imbalance, and their management must be started immediately while the results of investigations are being awaited. A stepwise treatment approach is as below:

Step 1: If the clinical examination and preliminary investigations do not reveal any evidence of infection then all antibiotics should be stopped. Oral feedings should also be stopped for 24–48 hours and the child should be put on intravenous fluids. By these measures alone, it is quite likely that diarrhea may stop. However, if it does not stop, one may think in terms of persistent gut infection, or a systemic infection, and therefore, systemic antibiotics may be needed. The antibiotics, which may be helpful in systemic infections, may be a combination of first- or third-generation cephalosporins with aminoglycoside. Occasionally, a fluoroquinolone group of anti­biotics may also need to be added. Metronidazole is not indicated in protracted diarrhea in children (contrary to the practice in adults). It can be given (7.5 mg/kg, three times a day orally for 5 days) when the microscopic examination of fresh feces reveals trophozoites of Entamoeba histolytica within red cells or two different antibiotics, which are usually effective for Shigella locally, have been given without clinical improvement. For giardiasis, metronidazole is given in the dose of 5 mg/kg, three times a day for 5 days if cysts or trophozoites of Giardia lamblia are seen in the feces.

Step 2: If the diarrhea recurs on reintroduction of milk, secondary lactose intolerance may also be considered as a possibility besides

65

ch-10.indd 65 18-12-2013 14:35:25 Clinic Consult: Childhood Diarrhea

the systemic infection. The child should be put on a low lactose diet for at least 3–5 days. If the child improves, then the amount of milk and other foods can be increased gradually in the diet.

Figure 1 Chronic diarrhea: management algorithm.

66

ch-10.indd 66 18-12-2013 14:35:25 Persistent/Protracted/Recurrent/Chronic Diarrhea

Step 3: If the child fails to tolerate even “low lactose” feeds, then it is prudent to stop the milk completely because it might also be because of CMPI. The child may then be put on a rice dal, khichdi, soya milk type of diet. If this child improves, then it is recommended that this diet should be given for at least 4–6 weeks, and milk should be reintroduced in their diets in a very careful manner later on. Most of the children might require a milk-free diet for at least 8–12 months.

Step 4: If the child does not respond to any of the above steps, then it may have to be put on intravenous (parenteral alimentation). Most of these children have multiple vitamin and mineral deficiency besides the PEM. Zinc deficiency is particularly more marked in protracted/chronic diarrhea. It is believed to be a major factor in prolongation of diarrheal episode. Therefore, these children should receive multivitamins and zinc in therapeutic regimes (Figure 1).

key messages

‰‰ Prolongation of diarrheal episodes associated with failure to thrive need to be addressed ‰‰ Persistent colonization of upper small intestine, dietary allergies, decreased host immunity, malnutrition, poor hygiene, food conta­ mina­tion, and protozoal infections are some common causes of pro­trac­ted/recurrent/chronic diarrhea ‰‰ Treatment focuses on providing adequate calories, low lactose load, antibiotics in case of gut or systemic infections, multivitamins, and mineral supplements ‰‰ When unresponsive, it might be necessary to rule out lactose into­ lerance, CMPI, and celiac disease.

67

ch-10.indd 67 18-12-2013 14:35:25 CHAPTER 11

Celiac Disease

This is due to gluten (gliadin part) induced enteropathy. It is an autoimmune type of chronic inflammatory condition. It is being more frequently diagnosed in India due to wheat becoming a major part of the food menu. It usually manifests in children beyond infancy as the introduction of gluten-containing foods occurs in such children. The manifestations are chronic diarrhea, failure to thrive, pallor, and short stature as the common features. Various other defects in absorption may also become clinically manifest like iron and B12 deficiency. Sometimes it may present as a case with profuse diarrhea leading to dehydration, acidosis, and shock (celiac crisis). Provisional diagnosis is by getting positive immunoglobulin A (IgA) isotype serological markers, serum antigliadin (AGA), tissue transglutaminase antibody (tTG), or anti-endomysial antibody (EMA). The AGA is not the preferred test, but in 25% cases, tTG may be negative, and it is in these cases where the AGA may help. The confirmation is by endoscopy and jejunal biopsy, which show subtotal villous atrophy. This investigation is mandatory. The management is by complete withdrawal of wheat and other sources of gluten (e.g., rye, barley) for the whole life. Initial relief may tempt to reintroduce wheat in the diet. This can be self-defeating and increases the risk of non-Hodgkin's intestinal lymphomas and

ch-11.indd 68 18-12-2013 14:35:51 Celiac Disease

neurological disorders like ataxia, peripheral neuropathy, migraines, and depression. Hypocalcemia, rapid weight loss, or no response to gluten-free diet may require corticosteroids. Associated lactose intolerance, which is also common, should be taken care of. Vitamin, mineral and iron supplementation is also indicated. A Swedish study showed that the possible cause of increased incidence of celiac disease can be due to early stoppage of breastfeeding and early introduction of cereals. The breast milk provides an immunological umbrella at the time of weaning. The study recommended that the breastfeeding should continue while weaning is being done and cereals should not be introduced before 4 months of life.

key messages

‰‰ Celiac disease is due to gluten-induced enteropathy ‰‰ Usually manifests beyond infancy with introduction of gluten- containing foods ‰‰ Provisional diagnosis is by serological markers and confirmation by endoscopy and jejunal biopsy ‰‰ Management is by complete withdrawal of wheat and other sources of gluten from diet.

69

ch-11.indd 69 18-12-2013 14:35:51 CHAPTER 12

Lactose Intolerance

Lactose intolerance is seen in children with persistent diarrhea. At times, sucrose, or very rarely, glucose intolerance can also occur. Although, lactose intolerance may be seen in the first 2–3 days of a watery diarrhea episode; at this stage, the intolerance is usually of not much significance, as it tends to be mild and transitory in nature. It often does not need milk withdrawal in majority of cases. On the other hand, lactose intolerance appearing after 5–7 days of a diarrheal episode may need specific management.

PATHOPHYSIOLOGY Lactose is a disaccharide unique to mammalian milk. It is hydrolyzed into the monosaccharide glucose and galactose at the brush border of enterocytes on the villous tip by the enzyme lactase (beta- D-galactosidase). Lactose appears to enhance the absorption of several minerals, including calcium, magnesium, and zinc. It also promotes the growth of Bifidobacterium and is a major source of galactose which is an essential nutrient for the formation of cerebral galactolipids. Low lactase activity in the small intestine allows undigested lactose to pass into the colon. In the colon, bacteria ferment the sugar to hydrogen gas and organic acids. The gas produces distention of the bowel, creating the sensation of bloating

ch-12.indd 70 18-12-2013 14:36:15 Lactose Intolerance

cramping and abdominal pain. Organic acids can be absorbed, but the quantity produced is rarely large enough to cause systemic symptoms or metabolic acidosis. Infectious diarrhea, particularly viral gastroenteritis in younger children, damages the intestinal mucosa enough to reduce the quantity of the lactase enzyme. Continued feeding with lactose- containing products often worsens and prolongs the course of the diarrhea. Instituting a lactose-free diet during moderate-to-severe gastroenteritis until the diarrhea has resolved is appropriate. Breast- feeding can usually be continued after a bout of gastroenteritis.

SALIENT FEATURES

Suggestive Clinical History • Frequent loose watery stools often with excessive flatus and associated with urgency that occurs several hours after the ingestion of lactose-containing substances is typical • Bloating, abdominal pain, and flatulence that occur from one to several hours after ingestion of milk or dairy products may signify lactose intolerance • Other disorders, which may cause similar symptoms, are milk– protein sensitivity, allergic-type reactions to other substances in the meal or other saccharide intolerance, recurrent abdominal pain of childhood and irritable bowel syndrome

Stool Analysis • Demonstration of reducing substances (++ or more) in the stool indicates that carbohydrates are not being absorbed. One common mistake, especially with superabsorbent diapers, is testing the solid portion of the stool instead of the liquid portion

71

ch-12.indd 71 18-12-2013 14:36:15 Clinic Consult: Childhood Diarrhea

• Reduced pH (<5.5) in freshly passed stools (within 15–30) minutes) is usually sufficient to establish a diagnosis of lactose intolerance. It is an indication of likely carbohydrate malabsorption, even in the absence of reducing substances.

Lactose Tolerance Test This is done by challenging the patient with 2 g/kg (up to 50 g) of lactose after a fast. If blood glucose does not increase more than 20 mg/dL and symptoms develop, a diagnosis of lactose intolerance is likely.

MANAGEMENT Lactose intolerance is a phenomenon related to quantification. Occurrence of diarrhea depends upon the amounts of lactose ingested. Reduction of dietary lactose instead of complete elimina­ tion often helps in overcoming the problem. Reduction in lactose content in an infant’s diet can be achieved by mixing milk with cereals and reducing the total amounts of milk to about 30–50 mL/kg/day. Giving curd in diet, instead of milk also helps in reducing lactose intake. The food can be made energy dense by adding suitable amounts of vegetable oils to the diet.

Low Lactose Foods • Milk-cereal (rice, wheat) mixture • Curd • Curd-cereal mixture • Mashed bananas. Examples of this food, which can be given to infants are kheer and dalia. Addition of sugar increases the caloric value.

72

ch-12.indd 72 18-12-2013 14:36:15 Lactose Intolerance

Lactose and Milk Protein-free Diet • Soya milk • Rice dal oil diet; e.g., khichdi • Soya nuggets and other food articles • Comminuted chicken.

key messages

‰‰ Mild lactose intolerance is seen with most watery diarrheal episodes in the first 2–3 days but is of not much significance ‰‰ Lactose intolerance appearing 5–7 days of diarrheal episode may need specific management ‰‰ Clinical history, stool analysis, and lactose tolerance test help in diagnosis ‰‰ Reduction of dietary lactose instead of complete elimination helps in treating the problem.

73

ch-12.indd 73 18-12-2013 14:36:15 CHAPTER 13 Cow’s Milk Protein Intolerance

It may be difficult to distinguish between cow’s milk protein intolerance (CMPI) and lactose intolerance, as the clinical features of both the conditions are similar, and the two causes may coexist. Cow’s milk allergic means allergy to the protein in cow’s milk. This may manifest with such symptoms as rash on the body, difficulty in breathing and swelling of the face and mouth along with excessive crying, vomiting or diarrhea. Children may be allergic to either or both the milk proteins, i.e. casein and whey. One may distinguish between milk protein intolerance and lactose intolerance by the fact that in milk protein intolerance the child gets diarrhea even on getting small amounts of milk or milk products, while in lactose intolerance the child is often able to tolerate reduced amounts of milk or milk-based diets, especially curd (dahi/lassi). One may reduce the milk content in diet, and if the diarrhea still persists, the diagnoses of CMPI should be considered. In this condition, there should be a complete withdrawal of milk and milk products. There is a cross allergy with soya milk protein in 30% of cases, and therefore, this substitution may also not be helpful.

ch-13.indd 74 18-12-2013 14:36:36 Cow’s Milk Protein Intolerance

key messages

‰‰ It may be difficult to distinguish between CMPI and lactose intolerance clinically ‰‰ The two conditions can also coexist ‰‰ In CMPI, the child is unable to tolerate even small amounts of milk ‰‰ In diagnosed CMPI, there should be a complete withdrawal of milk and milk products ‰‰ There is a cross allergy with soya milk protein in 30% cases of CMPI.

75

ch-13.indd 75 18-12-2013 14:36:36 CHAPTER 14 Vaccines Against Diarrheal Diseases

Two of the diarrheal conditions can be prevented by immunization, viz., cholera and rotavirus.

CHOLERA Vaccination against cholera was first tested in the 19th century and played a role in controlling epidemics. Injected (parenteral) whole- cell vaccines were used in the 1960s and 1970s, but they went out of favor, as their efficacy was found to be low (less than 50%) and short-lived (only 6 months). It had to be given every 6–12 months to maintain clinically significantly protection. They also had high rate of adverse effects and did not prevent transmission. They were withdrawn in 1970s. An effective inactivated whole-cell bivalent oral cholera vaccine against Vibrio cholera O1 and O139 has been used in Vietnam since 1990s. This has been introduced in India since the last few years. Results of the studies have shown that the vibriocial antibody response rate was 80% in children and 53% in adults. This vaccine gives over 60% protection against cholera. Duration of immunity and protection has been demonstrated to last for 3 years. It can be given in endemic setting to children aged 1.0–4.9 years who

ch-14.indd 76 18-12-2013 14:36:55 Vaccines Against Diarrheal Diseases

are at the highest risk of developing cholera. It is recommended to be given in two doses at 15 days apart in children above 1 year, vaccination to be repeated after 3 years. No serious adverse effects have been noted. Another vaccine which is a whole-cell killed oral cholera vaccine plus purified recombinant deoxyribonucleic acid (DNA) derived B-subunit of the cholera toxin has been developed in Sweden. This vaccine is effective against both the serotypes, Inaba and Ogawa and biotypes, Eltor and Classical. It needs to be coadministered with a relatively large volume of buffer solution. This Swedish vaccine is prohibitively expensive for use in developing countries. It is currently used in 60 industrialized countries and mostly by western tourists prior to visiting developing countries. It needs to be emphasized that the cholera vaccines are effective only in endemic situations. Once a cholera outbreak has begun, a vaccination campaign with a two dose vaccine is almost impossible and, therefore, of no use.

ROTAVIRUS Rotavirus is a major cause of diarrhea and the resultant mortality. It spreads mostly through person to person contact, and may be even by respiratory droplets. Therefore, it affects children of all socioeconomic strata and irrespective of hygienic or sanitary conditions. In India, it is estimated to cause 10 lac episodes of gastroenteritis, 2.5 lac clinic visits, more than 4.5–9 lac hospitalizations, and 1.2–1.53 lac deaths in under-five children every year. It costs the country nearly 250 crores rupees a year. Rotavirus leads to a profuse, explosive watery diarrhea also associated with vomiting, which makes oral rehydration difficult, and hence the need of hospitalization.

77

ch-14.indd 77 18-12-2013 14:36:55 Clinic Consult: Childhood Diarrhea

Currently two live oral vaccines are available globally: 1. Human monovalent live vaccine [Rotarix® by GlaxoSmithKline (GSK)]: R1 2. Human bovine pentavalent live vaccine (RotaTeq by Merck): R5. R1 contains one strain of live attenuated human strain 89-12 [type GIP1A (8)] rotavirus. It is in the form of lyophilized powder to be reconstituted with the liquid diluent before oral administration. After reconstitution, the vaccine should be administered promptly or kept in the refrigerator. If not used within 24 hours, it should be discarded. Each 1 mL dose is to be administered orally. The vaccine is to be given as two doses, the interval between these doses being at least 4 weeks. The earliest that the first dose can be given is 6 weeks and the latest time for this first dose is 12 weeks. The last dose should not be given after 8 months. R5 vaccine contains five reassortment rotaviruses developed from human and bovine parent rotavirus. It is in the liquid form. Each 2 mL dose is recommended to be given in a schedule of three doses with an interval of at least 4 weeks between each dose. The first dose should be administered at age 6–12 weeks and the last not later than 8 months (2 weeks). Thus vaccination with both these oral vaccines can began at 6 weeks of age (latest by 12 weeks) and should end by 8 months of age, the interval between the doses being at least 4–6 weeks. However, the IAP is of the opinion that if RV1 vaccine is to be administered in a 2-dose schedule, the first dose should start at 10 weeks of age instead of 6 weeks in order to achieve better immune response. The second dose can be administered at 14 weeks to fit with existing national immunization schedule. However, 3-dose schedule of any rotavirus vaccine can start at 6 weeks of age with minimum interval of 4 weeks between the doses.

78

ch-14.indd 78 18-12-2013 14:36:55 Vaccines Against Diarrheal Diseases

Giving the vaccine after the 8 months age may carry the risk of intussusception and hence it is not recommended beyond this age. Both vaccines should not be frozen. The vaccine should not be injected (such errors have happened). There is no need to readminister if a dose is spit out or regurgitated. Completing the course as per the schedule will take care of this problem. Ideally, the vaccine series should be completed with the same product (R1 or R5), but in case of unavailability of either vaccine, the course can be completed with the alternative product. Studies in South Africa and Bangladesh have shown that there is no reduction in efficacy when the rotavirus vaccines are coadminis­ tered with oral polio vaccine. Rotavirus should not be administered to infants with history of severe allergic reaction (e.g., anaphylaxis) to previous dose of this vaccine or a vaccine component. Latex rubber is a content of the R1 oral applicator. So infants with severe allergy to latex should not receive this human monovalent vaccine R1. The human bovine vaccine R5 dosing tube is latex free. A new rotavirus has been recently evolved in India. It is a live naturally attenuated vaccine, monovalent, bovine-human reassortant strain characterized as G9P[11], with the VP4 of bovine rotavirus origin, and all other segments of human rotavirus origin. The vaccine strain was isolated from asymptomatic infants, with mild diarrhea by Indian researchers in 1985 at All India Institute of Medical Sciences (AIIMS), New Delhi. Follow-up of these infants indicated that they were protected against severe rotavirus diarrhea for up to 2 years. This strain was sent for vaccine development to the National Institute of Health (NIH) by Department of Biotechnology (DBT), India and later transferred to Bharat Biotech International Limited in 2001 for further development. After phase III trials, the vaccine was launched in Delhi on May 14, 2013 in the name

79

ch-14.indd 79 18-12-2013 14:36:55 Clinic Consult: Childhood Diarrhea

of RotaVac®. It is now awaiting license from the Drug Controller General of India (DGCI).

MEASLES There is a strong relationship between measles and severe diarrhea. Measles immunization is a very effective method for reducing diarrheal morbidity and mortality, as it can prevent up to 25% of diarrhea associated deaths in children less than 5 years of age.

key messages

‰‰ Currently vaccination against diarrheal diseases is only available against cholera and rotavirus ‰‰ Cholera vaccines are effective only in endemic situations ‰‰ An oral inactivated whole-cell cholera vaccine is available in India, which is given in a two dose schedule for 15 days, apart in children above 1 year, repeated every 3 years ‰‰ Another parenteral cholera vaccine, which is a whole-cell vaccine plus purified recombinant DNA derived-B subunit of cholera toxin is available in the west ‰‰ Two live oral rotavirus vaccines are available ‰‰ The vaccination with both these rotavirus vaccines can began at 6 weeks and should end by 8 months of age ‰‰ Oral rotavirus vaccines can be given with oral polio ‰‰ Although not specifically an antidiarrheal vaccine, measles vaccination reduces diarrheal morbidity and mortality.

80

ch-14.indd 80 18-12-2013 14:36:55 Bibliography

1. Bhatnagar S. Antimicrobial in acute gastroenteritis. In: Shivananda, Yewale V, Prajapati B, Kundu R, editors. Handbook of Rational Antibiotic Therapy. Mumbai, India: IAP Infectious Disease Chapter Publication; 2009. pp. 15‑8. 2. Ganguly N. Cholera. In: Vashishtha VM, Kalra A, Thacker N, editors. FAQs on Vaccines and Immunization Practices, 1st edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2011. pp. 302-7. 3. Kliegman RM, Stanton BM, Geme JS, et al. Nelson Textbook of Pediatrics, 19th edition. Philadelphia, PA: Elsevier Saunders; 2011. 4. Mittal SK. Management of Acute and Chronic Diarrhea in Children, 3rd edition. New Delhi, India: CBS Publishers & Distributors; 2003. 5. Roy PK, Komanapalli SD, Shojamanesh H, et al. Lactose intolerance. [online] Available from: emedicine.medscape.com/article/187249-overview. [Accessed July, 2013]. 6. Sengupta A, Mannan M. Diarrheal diseases in children. Quart Med Rev. 2005;56(3):1-35. 7. Vashishtha VM, Kalra A, Bose A, Choudhury P, et al. Indian Academ of Pediatrics (IAP) Recommended Immunization Schedule for children Aged 0 through 18 years - India, 2013 and Updates on Immunization - Position Paper. Indian Pediatrics. 2013;50:1-18. 8. World Health Organization. Diarrhea. [online] Available from: who.int/ health-topics/diarrhoeal.htm. [Accessed July, 2013]. 9. World Health Organization. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Illnesses with Limited Resources, illustrated edition. Mumbai, India: Medica Press International; 2005. pp. 122-30.

Bibliography + guideline.indd 81 18-12-2013 14:37:27 Bibliography + guideline.indd 82 18-12-2013 14:37:27 Mission Statement: Clinic Consult

Series Clinic Consult

Objective The objective is to provide a ready reference tool with clinically relevant information that is up-to-date and presented in a clear, crisp, and reader- friendly format.

Target Audience The series would be targeted towards health-care professionals, registrars, and post-graduates in respective clinical fields.

Details Every subject-area has a series of topics which will be developed in to individual handbooks in a size of 5” by 7”and 8 to 12 chapters. The focus would be to provide information that can be referred to quickly during everyday clinical situations. The total word count would be between 20,000 to 25,000 words excluding tables, figures, images, etc.

Salient Features The selection of topics will be made in the order of everyday clinical importance. A smooth flowing easy-to-read format with abundant images, boxes, and tables would be used to summarize the topic without the need to consult various resources. Each chapter will have a list of key points which will highlight the salient points of the chapter followed by a list of suggested readings. Depending on the specialty, a series would have 8–12 topics which would be developed into individual titles.

Timelines The author/s would be expected to submit the manuscript in 4–6 months after finalizing the details. Every 2 to 3 years there will be revision of the titles in order to keep abreast with the clinical advances.

Bibliography + guideline.indd 83 18-12-2013 14:37:27 Bibliography + guideline.indd 84 18-12-2013 14:37:27