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REVIEW ARTICLE
Year : 2010  |  Volume : 17  |  Issue : 2  |  Page : 79-82 Table of Contents     

Oral rehydration salts, zinc supplement and rota virus vaccine in the management of childhood acute diarrhea


Department of Pediatrics, College of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia

Date of Web Publication23-Oct-2010

Correspondence Address:
Abdulwahab MA Telmesani
P.O. Box 13069, Makkah 21955
Kingdom of Saudi Arabia
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DOI: 10.4103/1319-1683.71988

PMID: 21359029

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   Abstract 

Acute diarrhea remains a major cause of morbidity and mortality in children. Since the introduction of oral rehydration salts (ORS) mortality has dropped to less than 50% worldwide. Low osmolarity ORS improved the outcome and reduced the hospitalization further. Zinc difficiency has been found to be associated with severe episodes of acute diarrhea. Zinc supplement in developing countries did reduce the incidence and prevalence of diarrhea. In addition, Zinc supplement significantly reduced the severity of diarrhea and duration of the episode. In the Americas and Europe, Rota virus vaccine was 90% effective in preventing severe episodes of severe rotavirus gastroenteritis. This review concludes that low osmolarilty ORS, zinc supplementation and rotavirus vaccine are major factors in reducing the morbidity, mortality and hospitalization resulting from to acute gastroenteritis in childhood.

Keywords: Diarrhea, childhood, oral rehydration salts, zinc, rota vaccine


How to cite this article:
Telmesani AM. Oral rehydration salts, zinc supplement and rota virus vaccine in the management of childhood acute diarrhea. J Fam Community Med 2010;17:79-82

How to cite this URL:
Telmesani AM. Oral rehydration salts, zinc supplement and rota virus vaccine in the management of childhood acute diarrhea. J Fam Community Med [serial online] 2010 [cited 2014 Sep 16];17:79-82. Available from: http://www.jfcmonline.com/text.asp?2010/17/2/79/71988


   Introduction Top


Acute diarrhea remains a leading cause of childhood deaths despite the undeniable success of oral rehydration therapy (ORT) over the years. [1] Since 1978, when the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) adopted ORT with oral rehydration salts (ORS) solution as the primary tool for fighting dehydration, the mortality rate of children under the age of five suffering from acute diarrhea has fallen from 4.5 million to 1.8 million annually. However, in spite of this impressive achievement, acute diarrhea remains a leading cause of death in children in developing countries. [2] Worldwide, 3-5 billion cases of acute diarrhea occur each year in children under 5 years. While global mortality may be declining, the overall incidence of diarrhea remains unchanged at about 3.2 episodes per child year. [3] Two main dangers of diarrhea are death and malnutrition. Death from acute diarrhea is most often caused by the loss of a large amount of water and salt from the body leading to severe dehydration. [4] Much has been done to lessen severity, shorten the duration and to prevent the occurrence of diarrhea, [5] but the three most important achievements in this field are low osmolarity ORS, zinc supplementation and Rota virus vaccine.


   Low Osmolarity Oral Rehydration Salts Top


After 20 years of research to improve ORS, a new formula has been developed and is recommended by WHO and UNICEF. [6] The efficacy of ORS solution for the treatment of children with acute non-cholera diarrhea has improved with the reduction of its sodium concentration to 75 mEq/l, its glucose concentration to 75 mmol/l, and its total osmolarity to 245 mOsm/l [Table 1]. The need for unscheduled supplemental intravenous therapy in children given this solution has reduced by 33%, stool output has reduced by about 20% and the incidence of vomiting by about 30%. [7] In a large multicenter trial of children with acute diarrhea not due to cholera, 675 children aged 1 to 24 months from 5 countries were randomized to receive standard or reduced osmolarity ORS. Although stool output and vomiting were not statistically different between the groups, the use of unscheduled intravenous fluids following initial rehydration was reduced in the group receiving reduced-osmolarity ORS (10% vs 15%) (odds ratio, 0.6; 95% confidence interval, 0.4-1.0). The occurrence of hyponatremia was not statistically different between the groups (11% in the reduced-osmolarity group vs 9% in the standard group) (odds ratio, 1.3; 95% confidence interval, 0.2-2.2). [9] In a meta­analysis of nine trials for the primary outcome, reduced osmolarity rehydration solution was associated with fewer unscheduled intravenous infusions compared with standard WHO rehydration solution (odds ratio 0.61, 95% confidence interval 0.47 to 0.81). Three trials reported that no patients required unscheduled intravenous infusion. Trials reporting secondary outcomes suggested that in the reduced osmolarity rehydration solution group, stool output was lower (standardized mean difference in the log scale - 0.214 (95% confidence interval - 0.305 to - 0.123; 13 trials) and there was less frequent vomiting (odds ratio 0.71, 0.55 to 0.92; six trials). Six trials sought the presence of hyponatraemia, with events in three studies, but there was no significant difference between the two arms. [10]
Table 1: ORS solutions developed by WHO[8]

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   Zinc Supplementation Top


Diarrhea with severe zinc (Zn) deficiency has been observed in children in developing countries. [11] These findings prompted studies of Zinc supplementation in children with diarrhea. Thus, there is a compelling body of clinical data that Zn is likely to be effective both in the treatment of acute diarrhea and in its prophylaxis. The results of studies on zinc treatment as an adjunct in acute diarrhea have been reviewed in many studies. [12],[13],[14] These randomized controlled trials using doses of zinc ranging from 10 to 30 mg per day were conducted in children aged between 6 months and 3 years. Zinc supplemented children had 15% faster recovery (95% CI 4% to 24%) with a 22% reduction (95% CI 9% to 34%) in the odds of acute episodes lasting more than seven days. Subsequent trials show results consistent with the meta analysis. [14] One study was of major interest as it measured the impact on stool output, the most objective marker of severity and a useful proxy indicator for risk of dehydration, in 286 hospitalized children with acute diarrhea and dehydration. [15] In the zinc treated children, the total stool output was reduced by 31% (95% CI 1% to 52%) than in the placebo group. All studies showed that the effect of zinc did not vary significantly with age, or the nutritional status assessed by anthropometry. The effects were not dependent upon the type of zinc salts used: zinc sulfate, zinc acetate or zinc gluconate. There was little gain in efficacy when the commonly used 20 mg daily dose of elemental zinc was increased to 30-40 mg daily. [12],[13],[14]

A pooled analysis of randomized, controlled trials of zinc supplementation performed in nine low-income countries in Latin America and the Caribbean, South and Southeast Asia, and the Western Pacific, demonstrated that supplemental zinc led to an 18% reduction in the incidence of diarrhea and a 25% reduction in the prevalence of diarrhea. [16] While the pooled analysis did not find differences in the effect of zinc by age, baseline serum zinc status, presence of wasting, or sex, the relevance of zinc supplementation to children in various geographic regions of the world remained unclear. Studies from Africa using zinc supplementation in 685 young children indicate significant benefit in the burden of diarrhea indicating that its effect may be consistent across various parts of the world, [17] even when administered with oral rehydration solution. [14] Recent studies in which zinc was used in the treatment of diarrhea in a community setting in Bangladesh (8070 children) also demonstrated a substantial reduction in concomitant use of antibiotics by health-care providers. [18] This suggests that there may be additional benefits with the use of zinc in the treatment of diarrhea.

Several changes have been found in Zn deficiency-associated diarrhea including morphologic changes in the intestine (e.g., villous atrophy, decreased brush-border activity, and altered intestinal permeability) and impairments of immune function (e.g., lymphoid tissue atrophy, reduction in lymphocyte count and T-helper cell proportion, cytotoxic activity of lymphocytes, and natural killer cell activity resulting in enhanced secretory response to cholera toxin. [19]

Despite several clinical observations of the efficacy of Zn in the treatment of acute diarrhea, the mechanism(s) by which Zn acts as an anti-diarrheal agent are poorly understood. [20] All of these successful clinical studies concluded that the possible mechanism for the beneficial effect of Zn on the duration of diarrhea included the following: (1) improved absorption of water and electrolytes by the intestine (undefined mechanism), (2) faster regeneration of gut epithelium, [21] (3) increased levels of enterocyte brush border enzymes [22] and/or (4) an enhanced immune response [23] leading to increased clearance of the pathogen(s) responsible for diarrhea from the intestine. [24]

A recent publication established that Zn inhibits cyclic adenosine monophosphate (cAMP)-induced complement one (Cl) secretion by inhibiting basolateral potassium (K) channels. [25] This study also showed the specificity of Zn to cAMP-activated Channels because Zn did not block calcium (Ca)-mediated K channels. Since this study was not performed in Zn-deficient animals, it provided evidence that Zn is likely to be effective in the absence of Zn deficiency. Another report recently provided evidence that Zn inhibits cholera toxin-induced, but not  Escherichia More Details coli heat-stable enterotoxin-induced ion secretion in cultured Caco-2 cells. [26]

Several other studies of potential action of Zn in cultured cell lines have been reported. [27] ,[ 28] One such report showed that micro molar concentration of extra cellular Zn triggered a massive release of calcium from intracellular pools in the colonocytic cell line. [27] If this observation is confirmed, one could argue that this sustained increase in intracellular Ca levels would enhance K efflux, leading to a hyperpolarization of cell membrane potential and the establishment of a favorable electrical gradient for Cl secretion.

Recently, WHO recommended that zinc supplementation should be provided at a dose of 10-20 mg per day for 10-14 days, and that this was efficacious in significantly reducing severity of diarrhea and duration of the episode. [29]

Zn is safe, well accepted, easily administered, and inexpensive. Most importantly, however, more laboratory-based studies that provide an understanding of the mechanism(s) whereby Zn is effective in the treatment of diarrhea are necessary. [20]


   Rota Virus Vaccines Top


Rotavirus is a leading cause of severe, acute diarrhea in infants and young children throughout the world, and is responsible for an estimated 527,000 deaths among children under the age of 5 years each year. More than 90% of childhood deaths attributed to rotavirus infection occur in developing countries, making prevention by vaccination a priority in such settings. [30] Available rotavirus vaccines are summarized in [Table 2].
Table 2: Live attenuated oral rotavirus vaccine[31]

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Large safety and efficacy trials conducted predominantly in the Americas and Europe demonstrated that both Rotateq and Rtoarix vaccines were highly (> 90%) efficacious in preventing severe rotavirus gastroenteritis. Neither vaccine was associated with intussusceptions. [32] While many countries quickly adopted a universal rotavirus vaccination policy, the absence of efficacy data from Africa and Asia precluded a recommendation for routine vaccination in those regions. The WHO, therefore, requested the testing of both vaccines in representative populations across both continents. In October 2005, a Phase III, placebo-controlled multi-centre clinical trial of Rotarix vaccine was initiated in South Africa and subsequently in Malawi. While the efficacy of the vaccine against severe rotavirus gastroenteritis was lower in Malawi than was observed in South Africa (77%), the public health impact of vaccination was likely to be great in Malawi because of the high incidence of severe rotavirus disease recognized during the trial. [33],[34]

Recently , The World Health Organization recommended that rotavirus vaccination be included in all national immunization programs in order to provide protection against the virus. [35]

Finally, low osmolarilty ORS, zinc supplementation and rotavirus vaccine are major steps on the road to decreasing the morbidity and mortality of acute diarrhea which is considered one of the most serious diseases affecting infants and children under five years.


   Acknowledgment Top


My thanks go to Dr. Hussein Koura for his critical revision of the article and Dr Maher Al-Zaiem for revising the Arabic translation of the abstract.

 
   References Top

1.Black RE, Morris SS, Bryce J. Where and why are 10 million children dying everyyear? Lancet 2003;361:2226-34.  Back to cited text no. 1      
2.Victora CG, Bryce J, Fontaine O, Monasch R. Reducing deaths from diarrhea through oral rehydration therapy. Bull World Health Organ 2000;78:1246-55.  Back to cited text no. 2      
3.Kosek M, Bern C, Guerrant RL. The global burden of diarrheal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 2003;81:197-204.  Back to cited text no. 3      
4.Bryce J, Boschi-Pinto C, Shibuya K, Black R. WHO estimates of the causes of death in children. Lancet 2005;365:1147-52.  Back to cited text no. 4      
5.WHO. The treatment of diarrhea: a manual for physicians and other senior health workers. 4 th rev. Geneva, Switzerland; 2005.   Back to cited text no. 5      
6.WHO. Reduced Osmolarity Oral Rehydration Salts (ORS) Formulation. New York, NY: UNICEF House; July 18, 2001. WHO/FCH/CAH/01.22.  Back to cited text no. 6      
7.Duggan C, Fontain O, Pierce NF, Glass R, Mahalanabis D, Alam N, et al. Scientific rationale for a change in the composition of oral rehydration solution. JAMA 2004;291:2628-31.  Back to cited text no. 7      
8.Bhutta ZA. Acute gastroenteritis in children. In: Nelson text book of pediatrics. Kliegman R, Behrman R, Jenson H ,Stanton B, editors. 18th ed. Saundres: 2008. P. 1614.  Back to cited text no. 8      
9.CHOICE Study Group. Multicenter, randomized, double-blind clinical trial to evaluate the efficacy and safety of a reduced osmolarity oral rehydration salts solution in children with acute watery diarrhea. Pediatrics 2001;107:613-8.  Back to cited text no. 9      
10.Hahn S, Kim Y, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review. BMJ 2001;323:81-5.  Back to cited text no. 10      
11.Bhal R, Bhandari N, Hambidge KM , Bhan MK. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting .Am J Clin Nutr 1998;68:414-7.  Back to cited text no. 11      
12.Zinc Investigators' Collaborative Group. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000;72:1516-22.  Back to cited text no. 12      
13.Black RE. Zinc deficiency, infectious diseases and mortality in the developing world. J Nut 2003;133:14855-95.  Back to cited text no. 13      
14.Bhatangar S, Bhandari N, Mouli UC, Bhan MK. Consensus statement of IAP National Task Force. Status report on management of acute diarrhea. Indian Pediatr 2004;41:335-48.  Back to cited text no. 14      
15.Bhatnagar S, Bahl R, Sharma PK, Kumar G, Saxena SK, Bhan MK. Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial. J Pediatr Gastroenterol Nutr 2004;38:34-40.  Back to cited text no. 15      
16.Bhutta ZA, Black RE, Brown KH. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators Collaborative Group. J Pediatr 1999;135:689-97.  Back to cited text no. 16      
17.Müller O, Becher H, Baltussen van Zweeden A, Ye Y, Diallo DA, Konate AT, et al. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomized double blind placebo controlled trial. BMJ 2001;322:1-6.  Back to cited text no. 17      
18.Baqui AH, Black RE, El Arifeen S, Yunus M , Chakraborty J, Ahmed S, et al. Effect of zinc supplementation started during diarrhea on morbidity and mortality in Bangladeshi children: community randomized trial. BMJ 2002;325:1059.  Back to cited text no. 18      
19.Roy SK, Tomkins AM. Impact of experimental zinc deficiency on growth, morbidity and ultra structural development of intestinal tissues. Bangladesh J Nutr 1989;2:1-7.   Back to cited text no. 19      
20. Kazi MH, Henry JB. Zinc in the Treatment of Acute diarrhea: Current Status and Assessment. Gastroenterology 2006;130:2201-5.  Back to cited text no. 20      
21.Bettger WJ, O'Dell BL. A critical physiological role of zinc on the structure and function of biomembranes. Life Sci 1981;28:1425-38.  Back to cited text no. 21      
22.Gebhard RL, Karouani R, Prigge WF, McClain CJ. Effect of severe zinc deficiency on activity of intestinal disaccharidases and 3-hydroxy-3-methy- glutaryl coenzyme A reductase in the rat. J Nutr 1983;113:855-9.  Back to cited text no. 22      
23.Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin 1998;68:447-63.  Back to cited text no. 23      
24.Fenwick PK, Agget PJ, McDonald D, Huber C, Wakelin D. Zinc deficiency and zinc repletion: effect on the response of rats to infection with strongyloids ratti. Am J Clin Nutr 1990;52:166-72.  Back to cited text no. 24      
25.Hoque KM, Rajendran VM, Binder HJ. Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum. Am J Physiol. 2005;288:956-63.  Back to cited text no. 25      
26.Berni CR, Cirillo P, Buccigrossi V, Ruotolo S, Passariello A, De Luca P, et al. Zinc inhibits cholera toxin induced, but not Escherichia coli heat stable enterotoxin induced,ion secretion in human enterocytes; J Infect Dis 2005;191:1072-7.  Back to cited text no. 26      
27.Hershfinkel M, Moran A, Grossman N, Sekler I. A zinc-sensing receptor triggers the release of intracellular Ca 2 and regulates ion transport. Proc Natl Acad Sci. 2001;98:11749-54.  Back to cited text no. 27      
28.Sheng S, Perry JC, Kleyman TR. Extracellular Zn activates epithelial Na 2 channels by eliminating Na 2 self inhibition. J Biol Chem 2004;279:31687-96 .  Back to cited text no. 28      
29. WHO/UNICEF. WHO-UNICEF Joint statement on the clinical management of acute diarrhea. Geneva, Switzerland: World Health Assembly, 2004.  Back to cited text no. 29      
30.WHO. Rotavirus vaccines. Wkly Epidemiol Rec 2007;82:285-96.  Back to cited text no. 30      
31.Cunliffe NA, Bresee JS, Hart CA. Rotavirus vaccines: development, current issues and future prospects. J Infect 2002;45:1-9.  Back to cited text no. 31      
32.Glass RI, Parashar UD, Bresee JS, Turcios R, Fischer TK, Widdowson MA, et al. Rotavirus vaccines: current prospects and future challenges. Lancet 2006;368:323-32.  Back to cited text no. 32      
33.Cunliffe N, Kirsten M, Madhi SA, Witte D, Ngwira B, Pieter Bos C, et al. Efficacy of human rotavirus vaccine RIX4414 in Africa during the first year of life. Ped Infect Dis J 2009;28:524.  Back to cited text no. 33      
34.Neuzil K, Madhi S, Cunliffe N. RIX4414 is protective against severe RVGE caused by diverse rotavirus serotypes during the first year of life in African infants. Ped Infect Dis J 2009;28:177-81.  Back to cited text no. 34      
35.WHO. Rotavirus vaccination. Wkly Epidemiol Rec 2009;84:232-6.  Back to cited text no. 35      



 
 
    Tables

  [Table 1], [Table 2]


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