Integrated Strategies of Chronic Diarrheal Disease in

The Control of Food and Fluid Intake in Health and Disease,edited by Michael J. G. Farthing and Dilip Mahalanabis. NestldNutrition Workshop Series, Pediatric Program, Vol. 51, NestecLtd., Vevey/Lippincott Williams & Wilkins, Philadelphia © 2003.

Integrated Strategies of Chronic DiarrhealDisease in Childhood

Abdul Majid Molla

Department of Pediatrics, Faculty of Medicine, University of Kuwait, Safat, Kuwait

DEFINITION

Chronic diarrhea can be defined as an episode of diarrhea continuing longer than14 days (1). In most cases it is associated with weight loss.

INTRODUCTION

Diarrheal disease still kills millions of children every year. Most of these inci-dences occur among the children of the developing countries. Because chronic diar-rhea originates from the episodes of acute diarrhea, it is important to consider thecauses, pathophysiology, and management of acute diarrhea. Therefore, this presen-tation while reviewing the causes and management of chronic diarrhea will initiallydiscuss the relevant issues concerning acute diarrhea especially in the context ofdeveloping countries.

It is estimated that 5% to 20% of acute diarrhea in children goes into a chronicstage (1,2). The global incidence of acute diarrhea is 1,000 million and accordingto a conservative estimate, the incidence of chronic diarrhea is 10 million per year.Approximately 67% of these children suffering from chronic diarrhea are malnour-ished. Thus, the combined affect of malnutrition and chronic diarrhea accounts forthe 40% to 60% of the total diarrheal deaths (3,4).

The causes of acute diarrhea in the developing countries are mainly infectious inorigin. While infectious diarrhea is mostly controlled in the developed countries,the causes of chronic diarrhea are due to emergence of some newer and rarer causes.Chronic diarrhea in the poorer countries is caused by prolongation or delayed recov-ery from acute infectious diarrheas. Those in the developed countries may includesome genetically linked conditions or some immunologically mediated conditionsor due to rarer causes of enzyme deficiency (5).

Table 1 presents some of the causes of chronic diarrhea. The list of organisms islonger for the developing countries compared to that of developed countries.

STRATEGIES OF CHRONIC DIARRHEAL DISEASE

TABLE 1. Causes of persistent diarrhea in the developing countries andindustrialized countries

Developing countries Developed countries

InfectiousRotavirus RotavirusEnteropathogenic EnteropathogenicEnteraggregative CryptosporidiumSalmonella sp. Food allergiesShigella sp. Autoimmune enteropathyClostridium difficile Cystic fibrosisGiardia intestinalis Microvillous inclusion diseasePost-diarrhea enteropathy Congenital chloride diarrhoea

Non-infectious Acrodermatitis enteropathicaCow's milk protein intolerance Glucose-galactose malabsorptjonLactose intolerance Enterokinase deficiencyMultiple food intoleranceCeliac disease

Special causesHIV infectionAutoimmune enteropathyEosinophilic gastroenteropathyMicrovillous enteropathyA-betalipoproteinemiaCongenital chloride diarrhoeaGlucose galactose malabsorption

RISK FACTORS OF CHRONIC DIARRHEA

Risk factors of chronic diarrhea are not yet completely known and some are stillbeing defined. In fact, a number of factors may be responsible for prolonging anacute episode of diarrhea into a chronic stage. Table 2 summarizes some of thefactors, many of which have been validated through careful research.

Age

Young infants seem to have more prolonged course of diarrhea in developingcountries. This is probably due to fecal contamination of food and water (3,6). Indeveloped countries, such evidence is scanty. This may be due to the fewer casesof infectious diarrhea in young infants in those countries.

TABLE 2. Risk factors of chronic diarrhea

Not definitely knownEnteric infection with virulent organismsMucosal injury due to infectionDelayed recovery of the mucosal injuryHost susceptibility, e.g., young age, malnutritionInappropriate initial managementRepeated attacks of acute diarrhea due to infectious organisms


Nutritional and Immunologic Status

Malnourished children tend to have more severe diarrhea of longer duration. Im-munocompromised patients are more likely to suffer from chronic diarrhea. Malnutri-tion diminishes the host defense to enteric infection, leads to a prolonged course,and may play a crucial role in causing death. A recent study in Bangladesh (7)showed that low weight for height resulted in 174% increased risk (relative risk= 2.74) of developing protracted diarrhea independent of age and immune status.Compromised immune status is yet another risk. Impaired cell-mediated immunitydoubles the risk of developing persistent diarrhea (8).

Type of Enteric Infection

Damage to the intestinal mucosa and its delayed recovery are central to the devel-opment of chronic diarrhea. Bacteria causing diarrhea may be classified as follows:

• mucosal adherent, enterotoxin-producing• brash border-effacing• mucosal-invading• mucosal-translocating and -proliferating in lamina propria• mucosal-penerrating, leading to generalized infection

Different infectious organisms involve different pathophysiologic mechanisms incausing diarrhea. Some of the organisms, for example, cholera and enterotoxigenicEscherichia coli (EPEC), elaborate enterotoxins without causing any morphologicabnormality (1,2). Activation of adenyl cyclase following binding of the toxin tothe receptor site of the enterocyte increases the intracellular cyclic-adenosine mono-phosphate levels, which in turn leads to massive secretion of fluid and electrolytes(9). Treatment of these types of diarrhea is replacement of fluid and electrolytesand continuation of the appropriate feeding. These types of diarrhea recover rapidlyand usually do not progress to a chronic stage. Shigella and EPEC invade the intes-tinal mucosa resulting in enterocyte death and mucosal ulceration (10). This typeof diarrhea resolves less quickly and may go progress to a chronic stage. Rotavirusdiarrhea is characterized by shortened villi, crypt lengthening, and an infiltrate ofthe lamina propria by inflammatory cells. Accelerated loss of enterocytes and then-replacement by relatively immature cells may lead to transient disaccharidase defi-ciency giving rise to osmotic diarrhea. Inappropriate use of antibiotics is likely tocause delay in recovery and a small percent may even progress to a chronic stage.Table 3 presents some of the enteropathogens isolated from the patients with chronicdiarrhea in Latin America (11).

Adequate Mucosal Recovery Is Prerequisite for Complete Recovery

The number of attacks of acute diarrhea in a year also plays an important role inthe duration of diarrhea. It has been observed that higher the number of attacks of


TABLE 3. Enteropathogens isolated during 1st week of illness in children with acute(< 8 days) and persistent diarrhea (> 14 days)

Enteropathogens

NegativeSalmonella sp.Shigelia sp.Campylobacter sp.Vibrio sp.Aeromonas sp.ETECEAECRotavirusGiardia intestinalisCryptosporidium sp.

No

80150255342

Acute diarrhea

%

33.304.2

20.80.08.3

20.820.812.516.78.3

Persistent diarrhea

No

602612

103081

%

2508.3

25.04.28.3

41.712.50.0

33.34.2

From Lanata(11).

FIG. 1. A case of chronic diarrhea and shigelia infection with kwashiorkor.

TABLE 4. Relation between number of episode in a year and the duration of diarrhea

No. of attacks inPrevious year

1-23-44+

No. ofepisodes

1255666205

Duration of diarrhea

<14d(%)

88.866.052.4

>14d(%)

11.234.047.6

From A. Ban etal. (II) 1988.


FIG. 2. Case of chronic diarrhea with marasmus (Bangladesh).

diarrhea, the longer the duration (12). Table 4 illustrates the relationship betweenthe number of attacks of diarrhea with recovery period. Figure 1 shows a child withchronic diarrhea who had four episodes of diarrhea in a year, one of which wasbloody mucoid that lasted longer than 3 weeks. Figure 2 shows another patient withchronic diarrhea with severe malnutrition.

INITIAL MANAGEMENT OF THE ACUTE DIARRHEAS

The initial management of acute diarrhea is vital because it determines how theacute episode will resolve. The initial management should include:

• rehydration using the most efficient type of rehydration fluid• appropriate nutritional management• justified use of antibiotics.

In a longitudinal study in Bangladesh, if cereal-based oral rehydration is used forthe early treatment of diarrhea the cumulative recovery rate was significantly highercompared to glucose-based oral rehydration or treatment with antibiotics and antidi-arrheal drugs (Table 5). For example significantly increased number of episodes (P< .0001) recovered on day 7 of treatment with rice-based oral rehydration solution(ORS) compared to glucose-based ORS or antibiotics. This was true for both waterydiarrhea and dysentery. Treatment with drags produced the least desirable result. Thisinformation provides an important signal. Treatment with antibiotics in shigellosis or


TABLE 5. Cumulative recovery rate from watery diarrhea among under five children usingdifferent treatment regimens

Treatment

Rice ORSGlucose ORSDrugsa

Rice ORSGlucose ORSDrugs

N

168714331827

733512689

Cumulative recovery rate, watery diarrhea (d)

3

65.930.5

5.9

18.57.12.8

7

Watery diarrhea

96.279.854.6

Dysentery

61.242.121.3

14

99.697.187.7

91.681.459.7

21

99.999.595.5

97.994.083.1

"Drugs included antidiarrheal drugs, antibiotics, and antiperistaltic agents as practiced by thevillage practioners.

other invasive infections leads to improved absorption of nutrients, more rapid recov-ery, and better weight gain (14). Even in very young infants (3 tol8 months), ORSprepared from rice syrup with the identical electrolyte composition resulted in supe-rior results compared to glucose ORS in terms of reducing stool volume and durationof diarrhea (15).

PATHOPHYSIOLOGY OF CHRONIC DIARRHEA

It is important to remember that it is not a single factor or even a group of definedfactors that result in chronic diarrhea. Chronic diarrhea is a complex interplay ofseveral factors such as host status, infection, several environmental factors and modeof treatment (16,17). We prepared a schematic representation of the factors contribut-ing to the production of chronic diarrhea, which is the result of an acute episode ofdiarrhea. (Fig. 3). It is clear from the hypothetical diagram that the opportunity toreduce progression to the chronic stage lies in the appropriate and adequate manage-ment of the acute diarrhea.

NEWER OR OTHER RARER GROUPS OF CHRONIC DIARRHEA

The list will remain incomplete unless a recently recognized group of conditionsis added. Of these, chronic diarrhea due to human immunodeficiency virus (HIV)infection needs special mention.

Acquired Immunodeficiency Syndrome Enteropathy

Diarrhea due to acquired immunodeficiency syndrome (AIDS) is common in theregions where AIDS-related diseases are frequently encountered (18). Patients withAIDS are immunocompromised and are vulnerable to diarrhea due to opportunistic


Enterie infections

yed recovery

Malabsorption of Nutrients Mucosal Enzyme deficiency

I iired villous repair • Carbohj

tin energy mal nutrition Osmotic

Impaired villous repair • Carbohydrate malabsorption

Protein energy mal nutrition Osmotic diarrhoea

Decreased bile salts Bacterial overgrowth

Chronic diarrhoea

FIG. 3. Schematic presentation of the sequence of events leading to chronic diarrhea.

organisms. These patients can have both watery as well chronic diarrhea due tomucosal injury (19). Organisms usually implicated are cryptosporidiosis and micro-sporidiosis. Recently, ADDS enteropathy, with mucosal injury has been describedwith no identifiable organisms. This probably implicates the HIV virus itself andits effects on the mucosal T cells (19,20).

In recent years in the Middle East, as well as in some other countries, .a certaintype of intractable diarrhea (some of them starting in early neonatal period) has beenidentified. During the past 5 years, we encountered these patients, who pose a seriouschallenge for diagnosis and management. Tables 6 and 7 present the diagnosis and

TABLE 6. Causes of intractable diarrhea in Kuwaitseen during the past five years

Diagnosis

Primary glucose-glactose intolerancelgG2 deficiencyTufting enteropathyMultisystem autoimmune diseaseAgammaglobulinemiaUndiagnosed

Total number

No.

326123

17


TABLE 7. Clinical characteristics of intractable diarrheapatients in Kuwait

GenderMaleFemale

ConsanguinityFirst cousinFar cousin

Family history of death due to diarrhea+ve- v e

Presenting symptomsVomitingDiarrheaFailure to thriveOnset <3 m

107

152

116

16151616

characteristics of these patients. It is clear that some of them are not amenable totreatment by any known mode of therapy. All of them require laboratory tests fordiagnosis, which are expensive and not widely available and most, if not all, requiretotal parenteral nutrition at the initial phase.

DIAGNOSIS AND MANAGEMENT OF CHRONIC DIARRHEA

Before initiating treatment, a correct diagnosis should be established. The causesof chronic diarrhea in infancy vary greatly compared to those in later childhood.Taking a good history is important. This should include information about diet,pregnancy, family history, weight, height, and other anthropometric measurements.Stool characteristics and some useful investigations should be performed in all thecases. Table 8 shows the laboratory tests that are useful. Once the results of thesetests are available, an approximate diagnosis can be made and an approach to themanagement can be undertaken.

Some major principles and the systematic management of chronic diarrhea aredescribed below.

1. Correction of fluid and electrolyte imbalance2. Treatment of life-threatening infections3. Nutritional management4. Use of trace elements where appropriate.

Fluid and Electrolyte Replacement

Most of these patients will pass several liquid or watery stools every day atpresentation to the physicians. Therefore, it is important to decide the degree ofdehydration and depending on this, rehydration should be initiated either by adminis-tration of an oral rehydration solution or by intravenous route using appropriate type


TABLE 8. Investigations necessary in a case of chronic diarrhea

1. Stool for microscopy >15-20 pus cells/hpF suggest invasive organismStool for pH s 5Reducing substances + + Suggest lactose intoleranceValidate with history and clinical signsStool for culture and sensitivity

2. Blood: Hemoglobin and Hb ^ 7 g/l may require urgent attentiontotal blood cell count &15,000 along with

&70% polymorphomuclear cells suggest infectionC-reactive protein >30 mg/ml suggest invasive organism

3. Electrolytes, blood urea nitrogen, and creatinineAny abnormality needs correction during early therapy

4. Sigmoidoscopy for local examination and for biopsy and culture5. Blood for total protein and albumin

Total protein <5 g/dl needs high protein dietAlbumin <2 g/dl needs high protein diet

6. Urine for routine tests and culture7. If systemic infection is suspected, proceed with the investigation accordingly8. Hydrogen breath test9. Absorption test:

Intestinal permeability test using non-absorbable sugars, e.g., lactulose/mannitol ratio10. Human immunodeficiency virus serology in areas of high suspicion index

of fluid. Patients with chronic diarrhea are usually deficient in potassium. Therefore,depending on the serum electrolyte levels, deficiency should be adequately corrected.This is especially true when intravenous solutions are used because many pediatricunits tend to use low sodium intravenous solutions without other electrolytes. Stan-dard intravenous solutions available in the hospital may not be sufficient to correctthe deficit.

Nutritional Management of Chronic Diarrhea

Dietary or nutritional management is the most important part of the managementplan and in most cases the failure of therapy is due to inappropriate use of unsuitablediets. Any fixed type of dietary regimen is not suitable for every child with chronicdiarrhea. A few important questions require answers before suggesting a suitabledietary regimen for chronic diarrhea:

• Are nutrients adequately absorbed from the traditional diets of the children in thedeveloping countries?

• Does the feeding during diarrhea adversely affect the course and outcome of diar-rhea?

The answers of these questions can be partially derived from some metabolicbalance studies carried out in developing countries (21).

Figures 4 and 5 presents absorption of macronutrients (carbohydrate, fat, andprotein) in acute diarrhea due to different etiology. Even in the acute stage of diar-rhea, the absorption of carbohydrate, fat, and protein is 84%, 66%, and 48%, respec-tively. Similar absorption rates were noticed in diarrhea due to other etiologies.

10 STRATEGIES OF CHRONIC DIARRHEAL DISEASE

100-

80-

60

CD

40

20-

m % Corbohydratto o Colonc

^ — ^ NiliO9*n

A R| R2

Different Stages of Diarrhea

FIG. 4. Absorption of macronutrients in rotavirus.

Following recovery from diarrhea, the absorption of all nutrients improved. Thiscan be explained by the fact that the pancreatic enzymes in acute diarrhea remainwithin the reference range and the digestive enzymes respond normally to stimulationby meals resulting in adequate digestion of food and absorption of nutrients (22).Another study in Bangladesh demonstrated that when the stooling rate in childrenwith cholera is 80 ml/kg/day, the absorption of carbohydrate is 64% and it decreasedto only 60% in high-purging patients; for example, 320 ml/kg/day when the childrenwere eating diets with rice, lentils, and chicken (23).

Recently, Isolauri et al.(24) studied intestinal permeability in three groups ofinfants with diarrhea using the lactulose-mannitol ratio in the urine after an oraldose of these nonabsorbable sugars. The patients were treated at home. One groupwas partially rehydrated using an oral rehydration solution and were not fed (groupA). The second group was fully hydrated but were not given food (group B). Thethird group was fully hydrated as well as fed with appropriate food (group C).Intestinal permeability improved most in group C and diarrhea recovered most rap-idly in this group.

Next question to consider is how common is lactose intolerance?Before 1970, lactose intolerance was common both in developing countries as

STRATEGIES OF CHRONIC DIARRHEAL DISEASE 11

100

60

s

40

20-

R, R2

Different Stages of Diorrheo

FIG. 5. Absorption of macronutrients in shigellosis.

well as developed countries. With the introduction of humanized infant formulas,the incidence of cow's milk protein intolerance or lactose intolerance has decreased(25). Several studies have shown that the duration on volume of diarrhea was notaffected when full-strength formula alone or combined with semisolid food was fedto the children with diarrhea (26). Based on these studies, starvation or regardingof milk feeds during acute diarrhea was abandoned (27). These recommendationsare valid in acute diarrhea in children, but chronic diarrhea is different and morecomplex.

Fortunately, data are available from few recent studies in chronic diarrhea fromthe developing countries.

In Bangladesh, Akbar et al. carried out a prospective study (28) in which milkwas the starting feed and 26% of children improved. A rice-based diet containingrice flour, egg white, oil, sucrose (or glucose), and electrolytes resulted in a 65%improvement in the children. A small percent (28%) required a milk-free diet. Thosewho were resistant to these diets were given a comminuted chicken-based diet withimprovement. Nizami et al. (29) used a traditional diet made of rice, lentils, andyogurt. Lactose-free formulas were given as a comparison diet. Compared to lactose-free formula, a significantly greater number of patients taking the rice, lentil, andyogurt diet improved within 4 days of starting the diet.


Other Adjuvant Therapy

In addition to the therapy described previously, there are a few helpful adjuvanttherapies in chronic diarrhea.

During the past decade, the addition of zinc in the treatment of diarrhea has gainedsupport . Roy et al. (30) measured intestinal permeability by the using lactulose/mannitol ratio 5 hours urine after an oral dose. Improvement in the intestinal perme-ability was noticed in the zinc-supplemented group in parallel with the increasedrecovery rate from chronic diarrhea. Sachdev et al. (31) noticed a shorter durationand decreased frequency of diarrhea in the zinc-supplemented group compared tothe control group. This is not difficult to imagine because most of the patientswith chronic diarrhea are malnourished and suffer from global nutritional deficiencyincluding trace elements. Another study in Bangladesh used a high-protein diet,providing 15% of calories from a protein source (compared to 7.5%), and demon-strated a significantly higher rate of weight gain (32). Thus it is important to supple-ment these patients with adequate micronutrients and trace elements specially thosewith malnutrition evident clinically and of longer duration.

GUIDELINES FOR DIETARY MANAGEMENT

Based on the investigations as suggested in Table 8 and the results obtained byvarious investigators in different countries, guidelines have been prepared for thedietary management of chronic diarrhea (Table 9). It is clear that even three or more

TABLE 9. Guidelines for the dietary management ofchronic diantiea

Diet A:Yogurt/Milk + Rice Suji + Oil + Sugar

Blend and store as packets of 150-200 ml.Feed every 4 hrContinue for 4 d

MonitorDaily weightStool outputHydration statusStool for pH and reducing substance

Criteria for failure:Increase in stool volume, frequencyVomiting and re-appearance of signs of dehydrationAfter 4 d if failure, change to diet B

Diet B:Rice + Chicken + Yogurt + OilCook and blendOffer 4-hr feedings

Monitor Same as aboveContinue for 4 dIf failure try diet C

Diet C: Comminuted chicken for 6-8 dIn case comminuted chicken failsTotal parenteral nutrition may be necessary


types of dietary regimens may not be sufficient. Therefore, careful monitoring andperseverance on the part of the physician and the family of the patients is necessary.

REFERENCES

1. World Health Organization. Persistent diarrhea in children in developing countries. WHO/CDD/88.27. Geneva World Health Organization, 1988.

2. World Health Organization. Diarrheal disease control: persistent diarrhea in children. WHO/CDD/DDM/85.1 Geneva. World Health Organization. 1985.

3. Fauveau V, Yunus M, Zaman K, et al. Diarrhea mortality in rural Bangladeshi children. J TropPediatr 1991; 37: 31-6.

4. Victoria CG, Huttly SR, Fuchs SC, et al. Deaths due to dysentery, acute and persistent diarrheaamong Brazilian infants. Acta Paediatr 1992; S381: 77-81.

5. Murch SH. The molecular basis of intractable diarrhea in infancy. In: Walker-Smith JA, ed. Bailliere 'sclinical gastroenterology. London: Bailliere Tindall, 1997: 413-40.

6. Cruz JR, Bartlett AV, Mendez H, et al. Epidemiology of persistent diarrhea among Guatemalan ruralchildren. Acta Paediatr 1992; S381: 22-6.

7. Baqui AH, Bradley Sack R, Black RE, et al. Cell mediated immune deficiency and malnutrition areindependent risk factors for persistent diarrhea in Bangladeshi children. Am J Clin Nutr 1993; 58:543-8.

8. Schloring JB, Me Ami JF, De Souza MA, et al. Malnutrition is associated with increased diarrheaincidence and duration among children in an urban Brazilian slum. Int J Epidemiol 1990; 19:728-35.

9. Cohen MB, Nogueiia J, Laney DW, et al. The jejunal secretory response to Escherichia coli heat-stable enterotoxin is prolonged in malnourished rats. Paediatr Res 1992; 31: 228-33.

10. Golberg MR, Sansonetti PJ. Shigella subversion of the cellular cytoskeleton: a strategy for epithelialcolonization. Infect Immun 1993; 61: 149-66.

11. Llanata CF. Acta Paediatr 1992; [Suppl]381: 32.12. Mavro MJ, Evans N, Me Neish AS, et al Intestinal damage in rotavirus and adenovirus gastroenteritis

assessed by D-xylose malabsortion. Arch Dis Child 1977; 52: 589-91.13. Bari A, Molla AM, Greenough WB m, et al Comparison of Rice ORS and glucose-ORS in Rural

Bangladeshi a field based longitudinal study 1991. AKU scientific series-p. 3.14. Molla AM, Molla AM. Effect of antibiotics on the food intake and absorption of nutrients in shigella.

Rev Infect Dis 1991; 13[Suppl]: 347-50.15. Rhoads JM. How super can super ORS get. J Pediatr Gastroentero Nutr 1992; 14: 240-3.16. Chronic diarrhea in children: a nutritional disease. Editorial. Lancet 1987; 1: 143-4.17. Mehta DL Lebenthal E, Blecker UWE. Chronic diarrhea: causes, presentation and management. Ind

Pediatr 1996; 63: 459-71.18. Guarino A, Spagnuolo MI, Russos J, et al Etiology and risk factors of severe protracted diarrhea.

J Pediatr Gastroenterol Nutr 1995; 20: 173-8.19. Pavia AT, Long EG, Ryder RW, et al. Diarrhea among African children born to HTV-I infected

mothers: clinical, microbiological and epidemiological features. Pediatr Infect Dis 11: 996-1003.20. Ullrich R, Riecken EO, Zeits M. AIDS enteropathy. Aim Intern Med 1991; 115: 328.21. Molla A, Molla AM, Sarker SA, Khatun M. Whole gut transit time and its relationship to absorption

of macronutrients during diarrhea and after recovery. Scand J Gastroenterol 1983; 18: 537-43.22. Molla A, Molla AM, Rahim A, et al. Effects of diarrhea on absorption of macronutrients during

acute stage and after recovery. In: Scrimshaw NS, Chen LC, eds. Interactions of diarrhea andmalnutrition. New York: Plenum, 0000.

23. Molla AM, Molla A. Does purging rate affect absorption of nutrients in diarrhea? Proceeding of the16th biennial international conference of Pakistan Paediatric Association. Feb 18—22,2002, Karachi,Pakistan.

24. Lauri E, Juntunen M, Wiren S, et al. Intestinal permeability changes in acute gastro enteritis: effectsof clinical factors and nutritional management. J Pediatr Gastroenterol Nutr 1989; 8: 466—73.

25. Walker-Smith JA. Cows milk intolerance as a cause of post enteritis diarrhea. J Pediatr GastroenteralNutr 1982; 1: 163-5.

26. Olson RE. Dietary recommendation of the American Academy of Pediatrics. Am J Clin Nutr 1995;61: 271-3.


27. Booth IW. Nutritional management of acute diarrhea. In: Walker-Smith JA, ed. Nutritional manage-ment of chronic gastro-intestinal diseases in childhood. New York: Raven, 1994.

28. Akbar MS, Roy SK, Banu N. Persistent diarrhea management: an algorithmic approach using a lowcost rice based diet in severely malnourished Bangladesahi children. / Trop Pediatr 1993; 39: 332-7.

29. Izami SQ, Bhutta ZA, Molla AM. Efficiency of a traditional rice-lentil-yogurt diet in managementof secondary lactose intolerance with acute childhood diarrhea. J Trop Pediatr 1966; 42: 133-7.

30. Roy SK, Behrens RH, Haider R, et al. Impact of zinc supplementation on intestinal permanentdiarrhea syndrome. / Pediatr Gastroenterol Nutr 1992; 15: 289-96.

31. Sachdev HPS, Mitral NK, Yadav HS. Oral zinc supplementation in persistent diarrhea in infants.Ann Trop Pediatr 1990; 10: 63-9.

32. Kabir I, Malek MA, Majumder R, et al. Rapid catch up growth in children fed with high proteindiet during convalescence from shigellosis. Am J Clin Nutr 1993; 57: 441-5.

DISCUSSION

Dr. Kaiser Ahmed: What's your experience regarding Giardia as a cause of chronic diarrheaand malabsorption, and what would be the management for a case of Giardia, where reoc-currence occurs and multiple recurrence occurs?

Dr. Abdul Majid Molla: I actually did not show any of the causes. Giardia has beenfrequently named, both in the developing countries and also in the affluent society, as a causeof chronic diarrhea, and I think it requires treatment and it gives very good results. It can bediagnosed by ordinary laboratory method.

Dr. Kaiser Ahmed: We find a lot of cases of Giardia, where recurrence occurs after treat-ment. Is there a treatment plan for those patients who reoccur?

Dr. Abdul Majid Molla: When I was working in Bangladesh, we used to see that kind ofgiardiasis, but that used to happen when they go back home to the same contaminated environ-ment and come back with giardiasis, that is, the recurrence of giardiasis, but each attack willlast longer whatever the cause and may need repeated treatment

Dr. Kaiser Ahmed: I would like to add one thing since we're talking about ORS so much,which is very, very important as a ground rule at the grass root level, and that is about thewater, which we are adding to the ORS and which is a very, very important contaminant.We may have good water supply in the cities, but looking at the rural areas, where even themedical people do not get potable water to drink, and is there a strategy for educating double-age health workers on this subject at the grass root levels, so that they advise mothers accord-ingly?

Dr. Abdul Majid Molla: I want to go back to the old issue of handwashing. In ICDDRBDr. Khan spoke about this and later on this study was carried out in different parts of theworld with very good success. We used to advise handwashing for the mother, after she hascleaned the child after defecation and also handwashing before preparing the food for thechild and, if possible, boiling the water, but boiling the water requires fuel, so in poor hygienicconditions it is a difficult thing, but by handwashing alone, it has been possible to cut downGiardia, shigella, and many of these infections. This one precaution is effective and simple.

Dr. Angha Jayakar. Which were the antibiotics you had used in your chronic diarrheapatients?

Dr. Abdul Majid Molla: I have not shown any antibiotic to be used in chronic diarrhea,because simply the fact is that the child, when he comes to you with chronic diarrhea, maynot have any culturable organism and so, unless you identify an organism which requirestreatment with antibiotic, we should not use antibiotics or antibacterials unless we can provetheir need.

Dr. John Matthai: A large proposition of patients with chronic diarrhea, especially the


young infants, have lactose intolerance. I find that in your slides you have recommendedmilk-cereal as the basis of treatment in chronic diarrhea. Is there a role for lactose? Don'tyou think a diet low in milk might be better?

Dr. Abdul Majid Molla: Milk is a very important part of the diet for growing children. Wecannot exclude milk altogether. The way I have taught, and people have worked with thisformula, is that if you give milk together with cereals, the effect of lactose on a low lactosestatus is not that bad and Dr. Ken Brown in Bangladesh has shown that, even if you givemilk to a lactose intolerant child or an adult along with cereals or rice suji as far as I amconcerned, they don't develop any symptoms, only lactose alone would cause symptoms, butif you mix it with other cereals, the symptoms will be reduced.

Dr. John Matthai: I am more concerned about the malnourished children, especially mal-nourished infants with chronic diarrhea. I think the incidence of lactose intolerance in themis high.

Dr. Abdul Majid Molla: This is what I showed that you try for 4 days, if they do notimprove after 4 days, switch to the next diet. In your last question which I would associatewith roundworm and vomiting, it is not a simple diarrhea, it is a complicated case so thechild will not go for oral rehydration, and you may treat him by intravenous fluid and thenimprove his condition before using anti-worm medicine. Your second question is that manyof the children come with acute diarrhea and then later develop a dysenteric type of diarrheaand whether to use antibiotics for this or not As a blanket rule, the over-use of antibioticsis not very wise, but if your situation changes and the child needs to use antibiotic, at thattime I think a stool microscopy would be very useful, and if you see parcels of more than15 to 25/high power field, the child is febrile and has got plenty of other clinical signs tosuggest that he has dysentery or a new infection, maybe at that time you can use the appropri-ately sensitive antibiotic or anti-parasitic drug.

Dr. Mohammad Juffrie: Sometimes in the pediatric ward, we found patients with immuno-compromise in relation with a protocol of cancer within long period. Because of the longstay in hospital then they developed into chronic diarrhea. Do you have an idea about howto treat those patients (immunocompromise chronic diarrhea)?

Dr. Abdul Majid Molla: This is again an entirely different ball game then the usual breadand butter of chronic diarrhea or any diarrhea, and the management of an immuno-compro-mised child per se is different from any other child with any infection, so I think it wouldbe very different unless Michael Farthing you want to add something? Immuno-compromisedchildren require a very different line of management, because you have to isolate them. Youhave to give them antibiotics for their infection, then you may have to give them immuno-globulin at a regular dose. It depends on what condition he is.

Dr. Michael J. G. Farthing: Majid, could you expand on the role of micronutrient deficiencyin persistent diarrhea and whether supplementation, either physiologically or super-physiolog-ically, in any way alters the course of the disease?

Dr. Abdul Majid Molla: There's a very nice slide I took out, because it required zincsupplementation. The only study that has been done on chronic diarrhea by Roy in Bangladeshand also in India, Sachader did quite a few elegant studies and in Pakistan, Dr. Bhutta. Iknew of these three studies. The recovery rate is 3 times more if you use zinc during thetreatment and illness duration becomes considerably and significantly shorter. Vitamin A,even in chronic diarrhea, has not been found to be useful in shortening the duration but inacute diarrhea, they found that there is some usefulness.

Dr. Suporn Treepongkaruna: In acute chronic diarrhea, small bacterial overgrowth mayplay a role in chronic diarrhea and if you cannot find the organism or find the pathogen, is


it reasonable to try to treat a small bio-bacterial growth for maybe 5 to 7 days? You mentionedabout the pathophysiology of the chronic diarrhea. One part of the pathophysiology is smallbowel bacterial overgrowth, and if this ensues with chronic diarrhea and we cannot find anypathogen, is it reasonable to try to treat small bowel bacterial growth, with for examplemetronidazole for 5 to 7 days?

Dr. Abdul Majid Molla: In case you suspect bacterial overgrowth, and you have tried allyour methods or possible lines of treatment, then of course you can use an antibiotic in someof the small groups of children. We have used them in the past, in Bangladesh as well as inPakistan, but that percentage is not very high. Even then there are groups of children whodo not respond to anything, but to diagnose as bacterial overgrowth, you need to do a lot oftests and if you suspect clinically when everything else fails, you can use some appropriateantibiotics, particularly metronidazole or something similar.

Dr. Dilip Mahalanabis: Let me add to what Dr. Molla said to the question you raised,because it is important, and also to one question regarding diet. Now regarding small bowelovergrowth, there is one study which compared bacterial overgrowth in persistent diarrheaand overgrowth in acute diarrhea. This was a study by Bardhan in Dhaka. This study showedno difference bwtween acute and persistent diarrhea, except for the type of bacteria in theupper small bowel. The second thing you need to consider is if repeated infection with entericpathogens rather than overgrowth is more important. The other is the multicenter trial, whichWHO conducted and it was done in Delhi by Dr. Bhan and Ashraf in Dhaka and a few otherplaces. It is a diet algorithm for persistent diarrhea, which used a graded diet starting withlow lactose (i.e., milk plus cereal), then a lactose-free improvised diet like whole egg or eggwhite with cereal and oil combination. If these diets do not work you go for comminutedchicken type of diet or specialized commercial diets. Now these studies were done with thisgraded dietary approach, particularly the diet with low lactose, on which most of them didvery well with simply grading those who failed to go to the next diet; the vast majority didexceedingly well with the standard milk cereal diet, which Dr. Bhan and Dr. Molla haveproposed. In this study the most unexpected finding was a large proportion of children havingsystemic infection of one kind or another, a much larger proportion than we expected, likethose with urinary tract infection, pneumonia, or otitis media, but particularly urinary tractinfection, which go unnoticed in this population. So you need to address this by treating moreof the systemic infection than perhaps the so-called bacterial overgrowth.

Dr. Anand Pandit. I think this sort of work was published way back in the late 1980s,when we finally perfected the chicken-based diet, which is now marketed in India and allover South Asia. This must be the last question: would there be any role for cholysteiaminein treating protracted diarrhea, especially in children.

Dr. Abdul Majid Molla: This is what I was going to answer also, that if you suspect thatthere is bacterial overgrowth, we have used cholysteiamine successfully, not necessarily thatall of it worked very well in all children, but in a very small percentage of children aftertrying everything, we have used with some success.

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